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Author
Topic: John2038's Research News (Read 226830 times)

HIV Infections In Hong Kong Reach Record LevelsHIV infections in Hong Kong have reached their highest ever levels. Four hundred and thirty-five new cases of HIV were recorded last year.

That's 5 percent more than in 2007 and the highest number of new cases since record keeping began in 1984, Department of Health announced yesterday.

Most of the 435 new infections were the result of sexual contact. Among those, 145 resulted from homosexual or bisexual partnerships and 131 from heterosexual contact.

Of the remaining new cases of HIV, 40 resulted from intravenous drug use and three were cases of blood infusion.

The causes of the remaining infections are unknown.

Wong Kah-hing, a consultant for the Centre for Health Protection's special preventive program, said sexual transmission continued to be the major cause in the spread of HIV in Hong Kong.

He urged those who do not practice safe sex to take an HIV test and start using condoms, China Daily reported.

"They should use a condom for safer sex to reduce the risk of contracting HIV," he said.

Department of Health figures showed that during the fourth quarter of 2008, 106 people tested positive for HIV.

The cumulative total of reported HIV infections in Hong Kong since 1984 is 4,047.

HIV is the viral infection that is at the root of AIDS. About half of HIV-infected people progress to AIDS within 10 years if the condition is not treated.

Loretta Wong, chief executive of AIDS Concern, an organization that provides AIDS prevention services said the high rate of HIV infection last year is a warning that AIDS prevention efforts in the past few years have proven insufficient.

Another reason for the increased number is that more people took the HIV test over the past year, she said.

She noted that the use of condoms to prevent the spread of AIDS is still not enough among the gay or heterosexual populations of Hong Kong.

She said about 60 percent of the gay population used condoms regularly.

"They know they should use a condom but they are willing to take risks when a condom is not available at hand," she said.

To reduce the number of HIV infections, she said social work organizations should increase AIDS prevention services.

This, she said, would require more government funding to make the services more stable and sustainable.

Getting funds is especially difficult in the current economic downturn so government help is really important for services working to prevent the spread of AIDS.

While public health campaigns remain largely focused on the young, the number of older people with the AIDS virus is continuously rising, global experts noted in an article published in the World Health Organization’s Bulletin.

“It's certainly true that we in public health concentrated our attention and efforts in terms of the AIDS epidemic and screening on younger individuals because those are the ones who are at most risk,” said Dr. George Schmid, a scientist with WHO's HIV/AIDS department in Geneva, and one of nine authors of the article.

This means that screening is not as readily encouraged for older people, which leads to a delayed diagnosis, decreasing life expectancy in people in this category of age. Whilst the life expectancy of those diagnosed with HIV between the ages of 5 and 14 is in excess of 13 years, this declines to 4 years for those infected after the age of 65.

According to the article in WHO’s Bulletin, studies in the US have seen an increase in HIV incidence in the over-50s from 20 percent to 25 percent between 2003 and 2006. In Brazil, the HIV infection rate in this category of age increased from 7.5 cases per 100,000 in 1996 to 15.7 cases per 100,000 in 2006.

What exactly has led to this increase? Scientists suggest that the availability of drugs treating erectile-dysfunction has extended the sex-lives of older people in the recent years. This goes hand in hand with a tendency for older individuals born in a world without AIDS not to practice safe sex.

“Physicians do not discuss sexual activity and risk factors for HIV infection nor are they as likely to suspect HIV infection in an older individual as much as they are in a younger individual … Physicians need to heighten their awareness that older individuals can well have risk factors for HIV infection and discuss those risk factors, including sexual activity with older individuals,” Dr. Schmidt said.

Another explanation could be that older people can be infected with the HIV virus much faster than young people due to a general decline in their immunity.

The authors of the paper noted that sexual activity remains the most likely mode of transmission for older people. However, more studies need to be done in order to establish the reason laying behind this worrisome increase in HIV cases among the elderly.

“We need to understand why and when these people are becoming infected so that public health campaigns can be better targeted to prevent such infections,” Dr. Schmidt said.

According to UNAIDS estimates, there are now 33.2 million people living with HIV, including 2.5 million children. Around 95 percent of people with HIV/AIDS live in developing nations. But HIV today is a threat to men, women and children on all continents around the world.

Tools For More Accurate Dosage Of Drugs Against HIV/AIDS And MalariaA doctoral thesis presented at the Sahlgrenska Academy, University of Gothenburg, Sweden, shows that it is possible to describe and quantify the relationships between dose, concentration and effectiveness of several drugs against HIV/AIDS and malaria. The method may allow improved treatment and fewer undesired effects for patients with these diseases.

New List Of HIV Mutations Vital To Tracking AIDS EpidemicIn a collaborative study with the World Health Organization and seven other laboratories, researchers at the Stanford University School of Medicine have compiled a list of 93 common mutations of the AIDS virus associated with drug resistance that will be used to track future resistance trends throughout the world...

To compile the latest list, the researchers added data from other laboratories in Europe, Canada and the United States to include more than 15,000 sequences from untreated individuals, double the number available in 2007. To ensure geographic diversity, information was included for eight different subtypes of the virus, as these vary from one region of the world to another.

The researchers scoured the data to ensure they included only those mutations that were clearly recognized as causing or contributing to resistance. They excluded polymorphisms, or variants of the virus that can arise naturally, as well as drug-related mutations that occur rarely.

The result was that 16 new mutations were added to the 2007 list, while three were dropped. Shafer said it was reassuring to find minimal changes were needed.

Drug Policies Could Condemn Millions To HIVAs governments meet next week in Vienna (11-12 March 2009) to set international drug policy for the next 10 years the International HIV/AIDS Alliance is concerned that HIV prevention strategies are being seriously undermined by conflicting policy approaches.

..

"Harm reduction groups from India to USA are harassed by the police at needle exchange sites and drug users are arrested attempting to access clean syringes. This simply makes users more likely to share needles. We need an environment that ensures that harm reduction strategies are not compromised and people can receive all the support they need to prevent themselves from contracting HIV and passing it to others," he said.

Notes

- HIV rates are just 1.1% in England and Wales among injecting drug users. In the USA where the federal government has not supported harm reduction approaches there is an estimated rate of 16%.

- 33 million people worldwide are estimated to be living with HIV.

- The International HIV/AIDS Alliance (the Alliance) is a global partnership of nationally-based organisations working to support communities to reduce the spread of HIV and meet the challenge of AIDS.

HIV cure needs to be scientific, funding priority, researchers and advocates warnA long-term public-private partnership should be developed to overcome barriers to a cure for HIV infection, a group of leading HIV researchers from academia and industry declare today in the journal Science.

Calling on colleagues, industry and donors to meet the challenge of curing HIV infection, the researchers say that exploring the possibility of engineering a drug-free remission from HIV replication – which probably requires complete elimination of the virus from the body – should be a priority.

"Without a vaccine, we are left with the substantial financial burden of lifelong treatment for tens of millions of people," said Professor Douglas Richman, director of the Center for AIDS Research at the University of California San Diego.

"Success – if achieved – will not occur quickly," Richman added. "But, bear in mind, the dramatic success of combination antiretroviral therapy which has transformed HIV/AIDS in the developed world and is beginning to impact the developing world required 15 years of substantial effort."

A similar call was recently issued by the Treatment Action Group, a US-based advocacy organisation, which recommended to the US National Institute of Allergy and Infectious Diseases that research into an HIV cure should be reinvigorated, with particular attention given to funding innovative investigators, developing animal models in order to learn more about HIV persistence and assays to measure latent virus and the effects of treatment.

"We are not going to find a cure for AIDS until we get serious and put it on the map," said Mark Harrington, executive director of TAG. "A collaboration between independent scientists and the drug industry is a practical proposal to get this research moving," said Harrington, welcoming today’s proposal.

Both groups propose that the goal of HIV therapeutics should be a drug-free remission – the long-term absence of detectable HIV replication without the need for ongoing treatment.

Achieving this goal requires understanding how HIV continues to persist at low levels in the bloodstream, and identifying all the reservoirs from which HIV continues to spring despite highly suppressive therapy, the researchers say.

In his recent plenary lecture at the Sixteenth Conference on Retroviruses and Opportunistic Infections Robert Siliciano presented evidence that currently available drugs are able to eliminate ongoing rounds of HIV replication, suppressing viral load below 1 copy per ml, and that any virus detectable in the bloodstream is likely to be the product of a previously latently infected cell.

However, intensification of therapy with currently available drugs did not seem to eliminate the release of virus from latently infected cells, suggesting, said Siliciano, that current treatment has reached its limit.

Siliciano explained that the cell reservoirs in which HIV persists in a latent form are still not fully understood. In addition the factors that keep HIV latent within those cells, often for many years, are not understood.

Better animal models, as well as human subjects for studies involving numerous intestinal and lymph node biopsies, are needed before the reservoirs are fully characterised and the mechanisms that maintain them understood.

Mechanisms for purging the reservoir need to identified and tested, an enterprise that will require screening of pharmaceutical compound libraries and substantial incentives for the private sector to develop research programmes.

The first major step towards reactivating the latently infected cells in the reservoir, Prof. Richman told aidsmap, is “identifying cellular targets which, if modulated, would activate only latently infected cells, since you can’t activate every cell in the body without killing someone. Step two is validating these targets in animal models and in drug discovery – hence the need for coordination.”

Tests that can accurately quantify very small amounts of HIV in tissues, which can measure latent HIV in one in a million CD4 cells and highly sensitive tests that can identify cells containing latent, integrated HIV provirus will be needed too, in order to measure the success of any therapeutic approaches.

The researchers making the case for a cure include David Margolis of the University of North Carolina at Chapel Hill, Warner Greene of the Gladstone Institute of Virology and Immunology, San Francisco, Daria Hazuda of Merck & Co, and Roger Pomerantz of Tibotec Pharmaceuticals. The longstanding AIDS treatment activist Martin Delaney, who died in January, was also an author of the article.

The call coincides with a huge funding stimulus for AIDS research, that will arrive in the form of a $10 billion uplift to the US National Institutes of Health budget approved as part of President Obama’s stimulus package.

Blogging at AIDSMeds.com, editor Peter Staley noted last week that HIV research could attract up to $1 billion of that allocation over the next two years, with new money likely to be devoted to expanding existing research programmes and funding well-reviewed applications that just missed funding in recent funding rounds.

But whether research into HIV eradication will be able to benefit from this stimulus is less clear. NIH issued a call for information about research priorities in the quest for HIV eradication last year, and is currently digesting responses. But at present the word `cure` does not feature in the NIH Office of AIDS Research list of critical AIDS research priorities for 2010, nor in its 2009 budget.

“It’s no wonder that scientists who apply for funding to study HIV latency are so often turned down: the term does not feature in the NIH plan,” commented Bob Huff of Treatment Action Group in the February edition of the group’s newsletter TAGLine.

However, persistence of HIV reservoirs will be one of a lengthy list of areas that will be given priority for funding under challenge grants being offered with stimulus package funding.

However, challenge grants will only last for two years, with work to be completed by 2011.

“The good news is, new money is coming. The bad news is, it's going away after two years with no guarantee of continuity unless the underlying NIH base budget, currently $30 billion a year, is increased, multi-year, over inflation,” commented Mark Harrington, Executive Director of the Treatment Action Group.

“So, the prospects of a big new cure project at this time are medium to low.”

Prof. Richman told aidsmap that a collaborative project was needed in order to prioritise and coordinate research.

“The funding that is available through the stimulus package is very restricted. It would be useful for investigators who want to look at individual targets but it doesn’t address the wider questions and the need for coordination.”

It is well known that tobacco smoking is a risk factor for lung cancer, cardiovascular disease, and other illnesses, and several surveys have indicated that people with HIV are more likely to smoke (50%-70% in some studies) relative to the general population (20%) -- a major concern since HIV positive people taking antiretroviral therapy (ART) are already at incraesed risk for these conditions.

At the 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009) last month in Montreal, Karen Tashima presented results of a study of a smoking cessation trial using a program designed for people with HIV.

Project Inform joins call for greater commitment and cooperation to identify a cure for HIV/AIDSA strong arsenal of antiretroviral medications has succeeded in making HIV a chronic but manageable disease for most people infected with the virus able to access them. But they do not actually cure HIV infection or AIDS. And so, a group of leading HIV experts has come together to call for a major new commitment and better collaboration among industry, academic, government and patient advocacy leaders to identify therapies that will actually cure HIV infection, or drive it into remission.

Among the experts calling for increased focus on a cure in the March 6, 2009 issue of Science magazine is Martin Delaney, the Founder of HIV patient advocacy group Project Inform. The article appears posthumously for Delaney, who died on January 26, 2009. Titled “The Challenge of a Cure for HIV Infection,” it is co-authored with three academics, Doug Richman of UCSD, David Margolis of UNC, Warner Greene of UCSF; one community advocate, Delaney; and two pharmaceutical industry leaders, Daria Hazuda of Merck and Roger Pomerantz of Tibotec.

“Current HIV medications have radically transformed the epidemic and restored or prolonged life for countless people. But the need for decades of their use by those patients who can actually get them is extremely expensive and their side effects can be profound,” said Dana Van Gorder, Project Inform’s Executive Director. “Good as they are, existing drugs are also incapable of eliminating latent reservoirs of the virus that go into deep hiding in the body. Novel new strategies must be developed to correct this problem. Today’s scientific goal must be to actually cure HIV infection or, perhaps more realistically, force it into a state of remission that will allow patients to stop taking antiretroviral drugs. Accomplishing this will be difficult, but not impossible, and demands a level of focus, collaboration and funding that does not currently exist.”

Inflammation, Cancers and Other Life Threats for People Living with HIVLost on the young but obvious to the old, is the fact we are not immortal. Those with chronic illnesses such as HIV infection are often all too well aware of the Damocles sword under which they live their lives. Fortunately, over the past decade or so mortality rates among HIV-positive persons in resource-rich nations have dropped. But, they remain in excess of those without the virus.

So, what do HIV-infected people die from in the era of potent antiretrovirals? What accounts for seemingly higher rates of disease associated with aging among those who are HIV-positive? Are "non-AIDS-related" conditions such as cardiovascular diseases and common malignancies actually a consequence of viral replication and/or relative immuno-suppression? These weighty questions were tackled by a number of presentations at this year's Conference on Retroviruses and Opportunistic Infections (CROI) and the data suggest that HAART may be an incredible savior but does not erase all the risks associated with HIV infection.

HIV-1 evolution in gag and env is highly correlated but exhibits different relationships with viral load and the immune responseObjective: To evaluate relationships between HIV-1 evolution, including immune evasion, and markers of disease progression during chronic infection.

Design: HIV-1 evolution and disease progression markers were evaluated over approximately 5 years of infection among 37 Kenyan women from a prospective, seroincident cohort. Evolution was measured in two genes, gag and env, which are primary targets of cellular and humoral immune responses, respectively.

Methods: Proviral HIV-1 gag and env sequences were obtained from early and chronic infection when plasma viral load and CD4 cell counts were available. Human leukocyte antigen types were obtained to identify changes in gag cytotoxic T-lymphocyte epitopes. The breadth of the neutralizing antibody response was measured for each woman's plasma against a panel of six viruses. Tests of association were performed between virus evolution (diversity, divergence, and ratio of nonsynonymous to synonymous divergence), markers of disease progression (viral load and CD4 cell count), and immune parameters (gag cytotoxic T lymphocyte epitope mutation and neutralizing antibody breadth).

Results: HIV-1 gag and env diversity and divergence were highly correlated in early and late infection. Divergence in gag was strongly correlated with viral load, largely because of the accumulation of synonymous changes. Mutation in gag cytotoxic T-lymphocyte epitopes was associated with higher viral load. There was evidence for adaptive evolution in env, but the extent of env evolution was only weakly associated with neutralizing antibody breadth.

Conclusion: Our results indicate that HIV-1 evolution in gag and env is highly correlated but exhibits gene-specific differences. The different immune pressures on these genes may partly explain differences in evolution and consequences for HIV-1 disease progression.

In an exclusive interview with the Hindustan Times, she said, "I guess we got the Nobel Prize after 25 years because by then we could see the benefit of the discovery on treatment of patients and prevention. Treatment of patients started in 1996 and some of the first patients who got a treatment are still alive"

"Patients with HIV AIDS are today living with the virus but our dream is to eradicate the virus. I am still working on it today because we don't have a vaccine and we need to improve the treatment," said Professor Francois Barre-Sinoussi who is here to attend the symposium on trends and specifications in HIV Infection Management organized by Fondation Merieux.

Professor Francois Barre-Sinoussi

She said, "HIV virus attacks our immune system. If you are infected by HIV, any infection you get you can die from it because your immune system is destroyed."

"The virus is capable of altering the function of our immune cells to respond to infection. We don't understand the precise mechanism of the virus as yet. This is the first virus I know which is doing this to our immune system. The virus is able to interrupt the dialogue between the cells as they communicate with each other."

Is a vaccine for AIDs in the horizon? "We don't know. It many take many years," said Professor Sinoussi who has been working on the virus for the past 25 years since she discovered it.

Even though there was a team working on locating the virus at Pasteur Institute in Paris, while others were conducting serological tests, Montagnier did the culture, she actually 'detected' the presence of the virus by looking at the enzyme activity caused by the virus, she said.

"Twenty five years ago, AIDS was a new epidemic and there were several hypothesis as to the cause of AIDS. At our Institute we were already working on retro virus (HIV is a retrovirus) which cause leukemia and cancer in animals and were rapidly within few were able to locate HIV. It is one of the first retrovirus known to affect humans," she said.

As a consequence of the discovery diagnostic tests for blood safety were developed as millions are infected by blood, by sex and drugs and from mother to the child.

She said her reaction to having found the virus was one "to rush and try to do whatever one could for the benefit of patients as there was an epidemic."

Her interest she said is only in the life and health of patients.

"If Indian scientists are focusing their attention on human disease, and science not for themselves but for patients then they have all the potential to succeed in winning more Nobel prizes ,"she added.

Background: Despite the widespread use of HAART in the United States, the mortality rate in HIV-infected individuals remains higher than in the general uninfected population. We compared the mortality risk of HIV-infected and control subjects and evaluated risk factors for mortality in subjects from the Study of Fat Redistribution and Metabolic Change in HIV infection (FRAM).

Methods: Vital status was ascertained in 922 HIV-infected men and women receiving clinical care and 278 controls enrolled in FRAM between 2000 and 2002. Analyses that compared mortality of HIV-infected to control subjects excluded HIV-infected individuals with recent opportunistic infection at baseline, and were restricted to the age range of controls (age 33 to 45, n = 468). Multivariable exponential survival regression was used to estimate hazards ratios (HR) for the: association of HIV infection with mortality after adjustment for demographic characteristics (age, sex, and race) and traditional cardiovascular disease (CVD) risk factors (smoking, diabetes, systolic and diastolic blood pressure, total and high-density lipoprotein [HDL] cholesterol), and association of HIV-related factors with mortality among HIV-infected subjects.

Results: After 5 years of follow-up, 12% of HIV and 2% of control subjects had died (HR = 6.9, 95%CI 3.0 to 16.1; p <0.0001). After multivariable adjustment, the hazards ratio for death was 3.4 (95%CI 1.3 to 8.5, p = 0.009). The figure shows mortality by time of attempted follow up in HIV-infected subjects stratified by baseline CD4 count and controls. Within HIV-infected subjects, the factors independently associated with death included current smoking (HR = 2.73 vs never smokers, p = 0.0001), increasing age (HR = 1.61 per decade, p = 0.0001), and low baseline CD4 count (HR = 0.65 per CD4 doubling, p <0.0001).

Conclusions: Mortality risk was 3 times higher among HIV-infected individuals than controls even after adjustment for demographic and traditional CVD risk factors. In addition to low baseline CD4 count, older age, and current smoking were strong and independent predictors of mortality in HIV-infected individuals.

Thanks President Obama !We surely need stem cells research to be made ! Hoping these research won't lead to any abuses of course.bloomberg

Obama to Restore ‘Science Integrity’ as Part of Stem-Cell Shift

March 9 (Bloomberg) -- President Barack Obama will reverse the U.S. government’s ban on funding stem-cell research today and pledge to “use sound, scientific practice and evidence, instead of dogma” to guide federal policy, an adviser said.

Harold Varmus, co-chair of a science advisory group to the President, said Obama will ask the White House Office of Science and Technology to create guidelines to incorporate ‘scientific integrity’ into decision-making by U.S. agencies. The action on stem cells, which can grow into any kind of tissue, may help speed research into cures for major illness.

Academic laboratories, led by Harvard University in Cambridge, Massachusetts, and companies already using stem-cell technology, led by Geron Corp., of Menlo Park, California, could gain tens of millions of dollars in funding because of the decision. A “significant amount” of $10 billion given the National Institutes of Health in Obama’s stimulus plan will go to this area of research, Varmus said.

“We view what happened with stem-cell research in the last administration as one manifestation of the failure to think carefully about how government use of scientific advice occurs,” said Varmus, a Nobel prize winner who is president of the Memorial Sloan-Kettering Cancer Center in New York, in a conference call with reporters yesterday. “Public policy must be guided by sound, scientific advice.”

The order involving embryonic stem cells will reverse a decision by former President George W. Bush to ban federal support for all but 21 cell colonies created before 2001.

Derived From Embryos

Stem cells derived from days-old human embryos have the potential to form any of the body’s 200 or so cell types, such as nerve cells or brain cells, and to repair or replace damaged tissue or organs. Adult stem cells, found in living tissue, have a more limited potential to become other cell types.

Bush said it was morally wrong to destroy embryos to develop stem cells. Researchers say that policy held back scientific advances and the development of cures.

“The Obama announcement will energize the stem-cell research community,” said George Daley, a member of the Harvard Stem-Cell Institute and researcher at Children’s Hospital in Boston. “The infusion of NIH funding from the stimulus package and the President’s endorsement will allow us to jump-start our projects. I am already getting e-mails from patients and colleagues applauding the decision.”

The elevation of science will extend beyond stem-cell research and into policies on health, energy and environmental programs, including global warming, said Melody C. Barnes, director of the White House Domestic Policy Council, who joined Varmus on the call with reporters.

120 Days

The National Institutes of Health, the government’s chief health-research agency, will have 120 days to develop new rules on stem cells, the White House said. Officials of the NIH have said they can prepare the guidelines more quickly than that.

The NIH has already begun requesting proposals for research projects using some of the $10 billion it was awarded from the economic stimulus.

“It’s fully anticipated that much of the stimulus money, a significant amount of it, will go to support work in this broad area,” said Varmus, who was director of the NIH from 1993 to 1999. Varmus was co-recipient of a Nobel in 1989 with J. Michael Bishop for their work on cancer genes.

Shares of stem-cell companies, which rallied in extended trading on March 6, after news of Obama’s decision became public, may gain further in today’s trading.

Opponents of the research consider embryos to be human life and research that destroys them to be immoral. They say stem cells from adult tissue and umbilical-cord blood are available without harming embryos and already in clinical use, while treatments from embryonic cells are years off.

Bush used the first televised address of his presidency, on August 9, 2001, to announce his policy banning the use of federal funds to support research on cell colonies, or lines, created after that date. Hundreds of newer lines can be used only by researchers funded from private sources.

Congress voted twice to overturn the Bush restrictions and Bush vetoed the measures both times.

Three-Year-Old Advance

A three-year-old advance allowed researchers to turn ordinary skin cells into powerful stem cells similar to those made from embryos. These cells, known as induced pluripotent stem cells, or IPS cells, were first created by Shinya Yamanaka, a researcher at Kyoto University in Japan.

Yamanaka left Japan on March 7 to fly to Washington to attend the signing ceremony today. Reached by telephone during a stopover in San Francisco, he said he supported President Obama’s decision.

“I thought I should accept this invitation because many people seem to think that because of IPS cells, embryonic stem cells are no longer required,” he said. “That is not the case.”

For Lauren Stanford, a 17-year-old high school student who was diagnosed with Type 1 diabetes at the age of 6, Obama’s order was the culmination of years of personal lobbying that has included testifying before the U.S. Senate and speaking at last summer’s Democratic National Convention.

‘Signing Hope’

“It’s like he’s signing hope for people with diabetes and other diseases into law,” Stanford said in a telephone interview. “I think hope can be a medicine too, it goes a long way in helping a kid whose life is very difficult to just feel a little better.”

Like most people with the Type 1 form of diabetes, Stanford must continuously monitor her blood-sugar level and inject herself with insulin several times a day to control her sugar levels. Type I diabetics don’t produce insulin, a naturally occurring hormone, and researchers have reported progress in their efforts to turn stem cells into insulin-producing cells that could be transplanted into the body.

Jonathan Slaek, director of the Stem Cell Institute at the University of Minnesota, said Obama’s action will enable researchers to use a wider range of cell lines, and also “improves the image of the USA.”

Diabetes Research

Researchers in Minnesota are studying insulin-secreting cells for treatment of diabetes, among other projects.

“The international perception is that there’s no stem-cell research allowed in America,” said Slaek, who is British. “In terms of scientific reputation and business climate, I think that message will probably be the most important.”

Still, bringing products to the market “is quite a ways away,” perhaps 10 years to 20 years, he said.

“We recognize there are a range of” religious beliefs concerning stem cell research and “a constant back-and-forth here,” said the White House’s Barnes. There is also a “a broad swath of the American public that does support the steps we’re going to take.”

The issue has become a key issue for some pro-life supporters.

“Taxpayer dollars should not aid destruction of innocent human life,” said House Republican leader John Boehner.

Vatican Response

In Rome, the Vatican’s newspaper deplored Obama’s reversal, repeating Catholic doctrine that such research in the eyes of the church is “deeply immoral,” the Associated Press reported.

Tony Perkins, president of the Family Research Council, called Obama’s planned reversal “a slap in the face” to Americans opposed to the destruction of human embryos.

“I believe it is unethical to use human life, even young embryonic life, to advance science,” Perkins said in a statement March 6. “While such research is unfortunately legal, taxpayers should not have to foot the bill for experiments that require the destruction of human life.”

HIV - Among the Greatest Battles In The History of HumanityA study published Wednesday in the journal Nature confirms the fact that the battle against the HIV virus is far from coming to a happy end. "It's very clear there's a battle going on between humans and this virus, and the virus is evolving to become unrecognized by the immune system," said Dr. Bruce Walker, one of the researchers and director of the Ragon Institute, at Massachusetts General Hospital in Boston. "It does make clear what a huge challenge making a vaccine is."

For instance, Last month the health ministry reported that the number of new HIV cases and AIDS diagnoses in Japan hit a high of 1,545 in 2008. According to the health ministry, 1,113 people were found to be infected with the HIV virus that can lead to AIDS, and 432 others were diagnosed with AIDS. This is the sixth consecutive year that a record number of new HIV cases has been reported, and the third straight year that a record number of AIDS diagnoses has been made.

In the meantime, health officials in northwest China are reporting a sharp increase in the number of AIDS cases being reported. The number of reported cases of HIV/AIDS rose by 50 percent last year to 216 in northwest China's Gansu Province. Fifty-five people already showed full-blown AIDS symptoms and 34 others had died of the disease in the past year, said Yu Ailing, head of STD/HIV/AIDS prevention at the GPCDC.

"The main reason behind the rising number of HIV/AIDS cases year on year lies in the fact the government has stepped up efforts to prevent and control the spread of HIV/AIDS, and tests and monitoring were tightened accordingly," said Yu.

Although treatments exist that can suppress HIV, there is no vaccine or cure. Prevention remains the only fully effective defense against the deadly virus. One doesn't have to "sleep around" to contract HIV; just a single exposure to the virus can result in infection. And because symptoms can take years to appear, many infected people are unaware they are carrying the virus. Ever since the AIDS virus was first identified more than 25 years ago, over 25 million lives have been lost because of the disease.

Throughout the study mentioned above, researchers from the Ragon Institute, Oxford University in England, Kumamoto University in Japan, and Royal Perth Hospital and Murdoch University in Australia analyzed the genetic sequences of HIV and human leukocyte antigen genes in 2,800 people total.

Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or breast milk. Within these bodily fluids, HIV is present as both free virus particles and virus within infected immune cells. The four major routes of transmission are unprotected sexual intercourse, contaminated needles, breast milk, and transmission from an infected mother to her baby at birth. Screening of blood products for HIV has largely eliminated transmission through blood transfusions or infected blood products in the developed world.

Africans and African-Americans progress to AIDS more slowly: strong association with hepatitis BTwo posters at the recent CROI conference, one from Europe and one from the USA, found that people with HIV of African descent have slower CD4 declines and progress more slowly to AIDS compared with people of European descent.

The European researchers suggest that immune-response priming due to exposure to other pathogens might be the reason why Africans progress more slowly, while the USA study found a strong association with hepatitis B infection; people who had caught hepatitis B and had either resolved it or had the chronic disease were more likely to be long-term non-progressors. They suggest that genes that are known to be associated with slow HIV progression may also make people more vulnerable to hepatitis B infection.

In the European study, the CD4 decline in patients of African and European descent in the Swiss HIV Cohort were compared. This ongoing study has recruited about 15,000 people with HIV since 1988 and currently contains about 7000 patients.

For the current study 463 European and 123 African patients were chosen and matched by age. Unusually for a cohort study the majority were women with three-quarters of African patients and nearly 60% of European patients female.

Africans had been infected on average for a shorter time (seven versus eleven years) and had a shorter time off antiretrovirals, during which CD4 counts were measured (average four versus five years). Average CD4 count at the time of cohort recruitment was 494 in Africans and 577 in Europeans.

The Africans had a twofold lower average viral load or ‘setpoint’ during the observation period (5300 versus 10250 in Europeans). They also had nearly half the rate of CD4 decline of the Europeans: the average annual CD4 decline was 28.2 cells/in Africans was 28.2 cells/mm3 in Africans and 52.5 cells/mm3 in Europeans.

The researchers analysed results according to HIV subtype, because in some other studies viral subtype has been associated with faster progression (although there were not enough patients with subtype D, which has been associated most often with fast progression). The subtypes analysed were A (most common in East Africa), B (predominant in Europe), C (mainly from southern Africa) and AG (west Africa).

The average viral load was at least 10,000 in every subtype analysed in Europeans and under 10,000 in every subtype in Africans. The highest annual CD4 decline per subtype was in subtype C in Europeans (80 cells/mm3) and subtype A in Africans (50 cells/mm3) while the lowest were subtype A in Europeans (45 cells/mm3) and subtype B in Africans (20 cells/mm3).

There was a relationship observed between setpoint viral load in Europeans and CD4 decline, but not in Africans. Every tenfold (1 log) increase in setpoint viral load in Europeans was associated with 42 more CD4 cells/mm3 lost per year, but viral load appeared to have no relationship with CD4 decline in Africans.

The researchers call their findings “remarkable” and hypothesise that one reason for slower progression in Africans might “reflect evolutionary adaptation to higher overall levels of antigenic exposure in Africa”. In other words Africans may be more likely to have genes that became predominant in response to other tropical infections and confer a degree of resistance to HIV.

The other study presented tended to support this theory by finding that African Americans had slower HIV progression than other ethnicities and also tended to have specific genes associated with slower progression. It also uncovered a remarkable and very strong association with hepatitis B infection.

The Multicenter AIDS Cohort Study (MACS) is the oldest HIV cohort study in the world; since 1984 it has recruited over 7000 originally HIV negative gay men and observed average time to HIV infection and the subsequent course of disease.

For this study it compared 55 Long Term Non Progressors (LTNPs) with 179 “Expected Progressors” (EPs). The definition used for LTNPs was that none of them had progressed to an AIDS-defining illness 15 years after infection, while EPs had all progressed to AIDS by their twelfth year of infection. The LTNPs were observed out at far as 22 years after infection, by which time two people had developed AIDS. In the EPs the shortest time to AIDS was three years and the median time about 6.5 years.

A number of factors were associated with being an LTNP. The first was age at infection: 60% of LTNPs were aged 25-35 at infection compared with 45% of EPs; in contrast 13% of EPs were over 45 at infection compared with 2% of LTNPs (just one person).

The second was African ethnicity. Nearly a quarter (22%) of LTNPs were African-American compared with just 4% of EPs. This was highly statistically significant (p=<0.001).

This was a striking enough finding, but what was also unexpected was the association with hepatitis B. Nearly three-quarters (73%) of LTNPs versus 42% of EPs, had had hepatitis B and had resolved it, i.e. had cleared the virus and had protective antibodies to it. In contrast 22% of LTNPs and 56% of EPs had either never been infected with hepatitis B or had been vaccinated against it. In addition 5% of LTNPs had chronic hepatitis B infection versus 1% of EPs but the numbers here were too small to be significant. The same associations were not seen with hepatitis C infection or with HHV-8, the virus that causes Kaposi’s sarcoma.

The researchers also found three specific immune-system genes to be associated with slow progression, none of them unexpected. These were the B57* HLA gene also associated with abacavir hypersensitivity (30% of LTNPs versus 6% of EPs), one copy of the CCR5d32 delete gene (37% of LTNPs versus 13% of EPs) and another chemokine-receptor gene called RANTES-403A.

The researchers note that these genes “have also been associated with recovery from hepatitis B infection”, though why slow progression should be associated with higher rates of hepatitis B infection in the first place is unclear. Vaccination could be a confounder (as indicating white ethnicity), or the same genes that confer resistance to HIV progression might also confer vulnerability to hepatitis B.

That article mentioning the piece in Nature about HIV being among the greatest battles in the history of humanity at first sounded very depressing but I read further and here's what one scientist involved had to say:

‘Where a favourable HLA gene is present at high levels in a given population, we see high levels of the mutations that enable HIV to resist this particular gene effect,’ says author Professor Rodney Phillips, co-director of the James Martin Institute for Emerging Infections at Oxford University. ‘The virus is outrunning human variation, you might say.’

‘The temptation is to see this as bad news, that these results mean the virus is winning the battle,’ says Professor Goulder. ‘That’s not necessarily the case. It could equally be that as the virus changes, different immune responses come into play and are actually more effective.’

How Inflammatory Disease Causes Fatigue: chronic inflammation infiltrates the brain but can be blockedNew animal research in the February 18 issue of The Journal of Neuroscience may indicate how certain diseases make people feel so tired and listless. Although the brain is usually isolated from the immune system, the study suggests that certain behavioral changes suffered by those with chronic inflammatory diseases are caused by the infiltration of immune cells into the brain. The findings suggest possible new treatment avenues to improve patients' quality of life.

Chronic inflammatory diseases like rheumatoid arthritis, inflammatory bowel disease, psoriasis, and liver disease cause "sickness behaviors," including fatigue, malaise, and loss of social interest. However, it has been unclear how inflammation in other organs in the body can impact the brain and behavior.

The researchers found that in mice with inflamed livers, white blood cells called monocytes infiltrated the brain. These findings support previous research demonstrating the presence of immune cells in the brain following organ inflammation, challenging the long-held belief that the blood-brain barrier prevents immune cells from accessing the brain.

"Using an experimental model of liver inflammation, our group has demonstrated for the first time the existence of a novel communication pathway between the inflamed liver and the brain," said the study's senior author Mark Swain, MD, Professor of Medicine at the University of Calgary.

Swain and his colleagues found that liver inflammation triggered brain cells called microglia to produce CCL2, a chemical that attracts monocytes. When the researchers blocked CCL2 signaling, monocytes did not enter the brain despite ongoing inflammation in the liver.

Liver inflammation also stimulated cells in the blood to make an immune chemical (TNFa). When the researchers blocked the signaling of this immune chemical, microglia produced less CCL2, and monocytes stayed out of the brain..

In the mice with inflamed livers, preventing the entry of monocytes into the brain reduced sickness behaviors; mice showed more mobility and social interaction. These findings suggest that people with chronic inflammatory diseases may benefit from treatments that limit monocyte access to the brain.

"Sickness behavior significantly impacts quality of life. Our findings further our understanding and may generate potential new avenues for treatment of these often crippling symptoms," said Swain.

"The brain is the master coordinator of many of our bodies' defense responses, so it must be able to sense injury and inflammation in distant body organs. This study starts to explain the peripheral communication signals that activate the brain," said Nancy Rothwell, PhD, DSc, at the University of Manchester, an expert on brain inflammation who is unaffiliated with the study.

The research was supported by the Canadian Institutes of Health Research, the Canadian Liver Foundation, and the Alberta Heritage Foundation for Medical Research.

Quantification of HIV Tropism by "Deep" Sequencing Shows a Broad Distribution of Prevalence of X4 Variants in Clinical Samples that Is Associated with Virological OutcomeBackground: "Deep" sequencing (Roche GS-FLX) detects minority HIV variants in clinical samples. Here, we performed both deep and standard sequence analyses of the HIV V3 region from individuals entering a clinical trial of maraviroc, all of whom had evidence of X4/DM virus and would not be expected to show a virological response.

Methods: Screening samples from the Pfizer A4001029 study were polymerase chain reaction (PCR) amplified in triplicate (n = 202). Tropism phenotype of all samples was X4 or DM by the standard Monogram Trofile assay as defined by the study entry criteria. Conventional (n = 153) and "deep" sequencing using the GS-FLX was performed using a "barcoding" approach, allowing the simultaneous analysis of 48 samples in both directions (n = 202) in a blinded manner. V3 genotypes were interpreted using the PSSM and/or geno2pheno algorithms.

Results: An average of >4000 V3 sequences were obtained from each sample. All samples had detectable levels of X4 HIV by deep sequencing, with 4% of patients having ?1% inferred X4 by PSSM, 14% having 1 to 10% X4, 50% having 10 to 90% X4, and 31% of patients having more than 90% X4. Tight correlations were generally observed between the forward and reverse sequencing directions, with <4% coefficient of variation.. The percentage of X4 determined was generally similar whether the PSSM or geno2pheno interpretations were used, (72% of samples fell within 4% of each other), despite some large outliers. Standard sequence analysis failed to detect X4 in 28% of samples. This was primarily driven by the low prevalence of X4-samples which standard sequence detected as having X4 virus had a much higher proportion of X4 (median 78% X4; IQR 38 to 99% by "deep" analysis) compared to those missed by standard sequencing (median 9% X4; IQR 2.5 to 21%); p <<0.05. Preliminary analysis of viral load reductions in the twice-daily maraviroc arm showed greater response for those with <10% X4 by deep sequencing/PSSM (-1.8, -2.2, and -2.6 mean log changes at weeks 2, 4, and 8, respectively) compared to either those with >10% X4 or to those who received placebo. All of these showed <-1..75 log reductions at these points.

Conclusions: Deep sequence analyses detect and quantify low prevalence of X4 HIV within clinical isolates that are not detected by standard sequence analysis. A low prevalence of X4 was associated with improved virological response to maraviroc, even where standard Trofile indicated DM or X4 virus.

South Africa: Hundreds of thousands die due to delay in ARV rollout - StudiesThe latest edition of the HIV Treatment Bulletin contains a report on two studies calculating the excess number of AIDS deaths in South Africa resulting from a delay in governmental roll-out of highly active ARV treatment (HAART) and in preventing mother-to-child transmission (PMTCT).

Nattrass proposed that South African AIDS policy in the post-apartheid era has been a product of enduring hostility towards antiretroviral drugs (ARVs).

She said this approach initially stemmed from former President Thabo Mbeki's questioning of the science of AIDS, which developed into a marked resistance to the implementation of ARV-focussed prevention and treatment programmes. The persistent portrayal of ARVs as 'poison' by the then Health Minister, Manto Tshabalala-Msimang, did little to help the cause.

A Director of the AIDS and Society Research Unit (University of Cape Town) and Visiting Scholar with the Health Economics and HIV/AIDS Research Division (University of KwaZulu-Natal), Nattrass used demographic modelling to calculate the number of HIV infections and AIDS deaths that could have been prevented between 1999 and 2007, had the national government taken a more proactive stance.

The study suggests that if, during this period, the government had used ARVs for AIDS prevention and treatment at the same rate as in the Western Cape (from 10% in 2000 to 65% in 2007), which contravened the national ARV policy, then approximately 171 000 HIV infections and 343 000 deaths could have been prevented.

Nattrass also highlights the fact that the Medicines Control Council (MCC) and the Medical Research Council (MRC), two key scientific bodies, fall under the jurisdiction of the national Department of Health. Due to following a scientific approach to AIDS, both bodies, despite their theoretical independence, have suffered from political interference. Although the situation improved after 2006 when the responsibility for AIDS policy coordination was given to the Deputy President, the study underlines the importance of addressing South Africa's legacy of governmental undermining of the scientific governance of medicine.

Pride Chigwedere and colleagues at Harvard School of Public Health calculated the number of 'person-years' that could have been saved, had a feasible ARV programme been implemented in a timely fashion. The study, 'Estimating the Lost Benefits of Antiretroviral Drug Use in South Africa', is available at http://www.ncbi.nlm.nih.gov/pubmed/18931626.

By refusing to accept the scientific consensus that HIV causes AIDS, and by declining free donations of nevirapine and other resources from programmes such as the Global Fund and PEPFAR, the study estimates that the government contributed to the loss of 2.2million person-years (around 330 000 lives) between 2000 and 2005. 35 000 babies were born with HIV, because a PMTCT programme was not implemented. In total, the study estimates that approximately 3.8million people-years were lost in total during this period.

Public sector HAART in South Africa only moved beyond the pilot phase in 2004, with WHO estimates showing that HAART was scaled up from less than 3% in 2000 to 23% in 2005. The study suggests that an earlier state-implemented HAART programme of 5% coverage in 2000 could have been scaled-up to 50% in 2005 - a figure that would still be lower than the 85% coverage achieved in Botswana or the 71% in Namibia.

Both studies concur that government policy towards HIV/AIDS has proved a key, destructive factor in limiting the reach of both HAART and PMTCT.

Merck Will Buy Schering-Plough for $41.1 BillionMerck announced today that it is paying $41.1 billion in cash and stock for Schering-Plough (S-P), which manufactures the anti-HCV combination treatment regimen peginterferon alfa-2a (PegIntron) and ribavirin (Rebetol). S-P also brings cardiovascular, respiratory and oncology drugs to Merck's pipeline. Additionally, Merck says the merger with S-P will boost its presence in the biologics market.

Merck and Company is the manufacturer of raltegravir (Isentress), the first HIV integrase inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV infection. Integrase inhibitors work by preventing HIV from inserting its genetic material into host cells, thereby halting viral replication. Because integrase inhibitors work by a different mechanism than currently approved anti-HIV drugs, they are likely to work against virus that has developed resistance to other drug classes.

Boceprevir is a "STAT-C" agent, a drug that works directly against the life cycle of the hepatitis C virus. S-P has completed full enrollment in the HCV SPRINT-2 trial in which 800 mg thrice daily boceprevir is used in combination with PegIntron plus ribavirin.

Vicriviroc is a novel entry and fusion inhibitor that has shown promise in the treatment of HIV patients who are resistant to enfuvirtide (Fuzeon) and other antiretrovirals. The US Food and Drug administration has granted fast-track approval status to vicriviroc. Entry and fusion inhibitors act differently than other classes of anti-HIV drugs (e.g., protease inhibitors, nucleoside reverse transcriptase inhibitors) by preventing HIV from infecting and entering cells, rather than trying to eradicate HIV after the virus has infected a cell.

Both boceprevir and vicriviroc are considered promising new agents for the treatment of chronic hepatitis C and HIV infection, respectively.

Loss of kidney function is a concern for people with HIV, especially individuals of African descent. Several factors have been implicated in renal dysfunction, including HIV-associated immunodeficiency, viral replication, antiretroviral drug toxicity, and possibly inflammation and other poorly understood processes that result in higher rates of serious non-AIDS comorbidities.

GFR Changes in Treated and Untreated HIV Patients

To shed further light on these factors, Andy Choi and colleagues from the University of California at San Francisco compared rates of kidney function decline in 4 groups of HIV patients as defined by degree of viral replication in the presence or absence of antiretroviral therapy (ART):

* Untreated controllers (HIV RNA < 1000 copies/mL);

* Untreated non-controllers (HIV RNA > 1000 copies/mL);

* ART-treated controllers;

* ART-treated non-controllers.

As Choi described in an oral presentation at the 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009) last month in Montreal, the investigators estimated rates of change in kidney function among 615 participants enrolled in the SCOPE cohort.

Most participants (87%) were men, the mean age was 45 years, and they had relatively well-preserved immune function, with a mean CD4 count of about 430 cells/mm3. Participants were not excluded on the basis of existing kidney disease, nor were they stratified based on race (about half were white, one-third black).

Kidney function was estimated using the MDRD (Modification of Diet in Renal Disease) equation, which calculates glomerular filtration rate (GFR) based on age, sex, race, and serum creatinine.

Results

* In an unadjusted analysis, over a median 2.7 years of follow-up, the GFR change was -2.6 mL/min/1.73m2 per year in HIV positive people versus -0.4 mL/min/1.73m2 per year in the HIV negative population.

* Among patients first initiating ART, the rate of GFR decline slowed after starting therapy (+2.8 mL/min/1.73m2 per year).

* In a multivariate analysis adjusting for potential confounding factors, the rate of GFR decline was:

Based on these findings, the researchers concluded, "Although ART appears to help curb kidney function decline among those with uncontrolled viremia, patients who have achieved durable viral suppression continue to lose kidney function above age-expected norms."

"Overall kidney function loss is more closely associated with viremia, whereas the level of immunodeficiency (as defined by CD4 count) does not appear to be a major prognostic factor in either untreated or treated disease," they added.

Discussing the findings, Choi said that ART may reverse some kidney function decline, but it was "not completely benign," since treated HIV positive individuals still had greater decline than HIV negative people.

He added that his group plans to look more closely at inflammation, which may help explain the detrimental effect on kidney function of ongoing HIV replication.

Responding to a question about the significance of low viral load, Choi stated that "perfect controllers" with less than 50 copies/mL had a reduced rate of GFR loss compared to people with 50-1000 copies/mL.

He also noted that while the study was underpowered to analyze differences between specific antiretroviral drugs, there was no evident effect of any particular drugs, including tenofovir (Viread, also in the Truvada and Atripla combination pills) and indinavir (Crixivan).

Factors Associated with Kidney Function Decline

In the same session, Sonia Rodriguez-Novoa from Hospital Carlos III in Madrid, Spain, reported findings from a study that looked at genetic variations associated with tenofovir-related kidney tubule damage.

In some studies, tenofovir -- which is excreted by the kidneys -- has been associated with decreased kidney function, especially in people with pre-existing risk factors, although clinical kidney dysfunction was not observed in clinical trials that supported the drug's approval.

The mechanism underlying the effect of tenofovir on the kidney is not fully understood, but alterations in tubular transporter proteins may play a role. In this analysis, the investigators evaluated a range of single nucleotide polymorphisms (SNPs), or genetic changes at specific positions, on genes thought to code for relevant drug transporter proteins.

The study included 154 HIV patients taking tenofovir-containing ART regimens, 49 participants on ART without tenofovir, and 81 treatment-naive HIV patients. A majority were Caucasian. A subset of 115 tenofovir recipients were included in the pharmacogenetic analysis, 19 with and 96 without kidney dysfunction.

Altered kidney tubular function was defined as having at least 2 of the following: non-diabetic glucosuria (glucose in the urine), urine phosphate wasting, hyperaminoaciduria (elevated levels of amino acids in the urine), beta2-microglobulinuria, or increased fractional excretion of uric acid.

The researchers found that 22% of tenofovir recipients, 6% of patients on non-tenofovir ART, and 12% of treatment-naive individuals had kidney tubular dysfunction. Abnormal function was more common in people with the ABCC2-24 GG genotype than in those with genotypes GT or TT (24% vs 6%). Specific SNPs on the ABCC2 (aka MRP2), ABCC4 (MRP4), and SLC22A11 (OAT4) genes were linked to particular manifestations of kidney dysfunction.

"Genetic analysis of ABCC2-24 could help to identify patients at greater risk for renal tubulopathy," the investigators concluded. "Since [tenofovir] has been shown not to serve as a substrate for ABCC2, the precise mechanism of this association requires elucidation. Close monitoring of renal function is warranted in this subset of patients."

China plans to strengthen security along its borders with Central Asia to combat a rise in drug smuggling through its restive western region of Xinjiang, a newspaper reported Tuesday.

Xinjiang Governor Nur Bekri also said drug offenses were on the rise, and the increasing use of shared needles has given the region the highest HIV infection rate in the country, the China Daily reported.

Bekri said the region wants to beef up security forces along the border with the so-called Golden Crescent opium producing area of Central Asia, encompassing Iran, Afghanistan and Pakistan, the newspaper said.

"We have asked (the central government) for the deployment of more security forces. The current number is simply not enough," Bekri said.

Bekri said the number of border security staff has not changed since 1992 even though the number of travelers has increased from 69,000 a year to 2 million.

The report said half of the total drugs seized by Xinjiang police last year _ about 320 pounds (144 kilograms) of heroin and 15 pounds (6.7 kilograms) of methamphetamine _ came from the Golden Crescent.

"While traffickers are trying to make Xinjiang a transit point, consumption within the region is increasing as well," Bekri told the newspaper on the sidelines of China's annual legislative session.

The newspaper cited data from the Chinese Center for Disease Control and Prevention as showing that by September, about 25,000 cases of HIV infections had been reported in Xinjiang _ giving the region of 20 million residents the highest infection rate in the country.

To fight the increase in infections, Bekri said the regional government plans to allocate 40 million yuan ($5.8 million) to HIV/AIDS prevention programs this year.

He also reiterated earlier statements that officials were expecting further unrest this year in Xinjiang. Militant separatists among the region's native Turkic Uighur population allegedly carried out a series of deadly attacks last year as part of a long-simmering campaign against Chinese rule.

Authorities said they broke up other plots they claim were intended to sabotage the Beijing Olympics. They have responded to the threats with a massive security crackdown and big hike in arrests for state security crimes.

Culturally, religiously and linguistically distinct from the China's Han majority, Uighurs have long complained of economic marginalization by Chinese migrants who have flooded into Xinjiang since communist troops entered the region in 1949.

The crisis has led to massive job cuts and the "situation of migrant workers is under threat," according to the study, released in Manila by the United Nations Development Program, or UNDP.

"When demand for labor wanes, those in the weakest bargaining position, usually temporary migrant workers and particularly the undocumented, will accept almost any conditions to hold on to their jobs," the reports aid.

The reports said 70%-80% of migrants from Sri Lanka and the Philippines to Arab states were women. It said 60% of women migrants from Bangladesh also found employment in that region between 1991 and 2007.

But these women are now subjected to harsh realities, with many heavily indebted before leaving their home countries.

Others are subjected to sexual abuse by their employers, and fall prey to human traffickers.

"Conditions are expected to become harsher for even the employed migrant workers as they try to hang on to their jobs," said UNDP country representative Renaud Meyer, adding that among the most vulnerable were the illegals who would "accept almost any circumstances to hold on to their jobs."

"Worst still, during the present turmoil, desperation for work may lead to migration under unsafe conditions, sexual exploitation, and increased vulnerability to HIV infections," Meyer said.

While some countries require pre-departure orientation on HIV for migrants, many still remain uneducated about the virus, which causes AIDS.

In particular, 96% of Bangladeshi domestic helpers in the Middle East said they didn't receive such orientation before leaving home.

"While half of them have heard of HIV through the media or from coworkers, none had in-depth knowledge on HIV prevention and safe-sex practices," it said.

High recruitment fees and poor wages also push women migrant workers "into debt traps, which in turn, could lead to sexual exploitation."

"Those who flee abusive working conditions are immediately rendered illegal by host countries, exposing them to greater risk of abuse, including sexual exploitation and increased vulnerability to HIV," the study said.

The study was based on more than 600 interviews with migrants from the Philippines, Sri Lanka, Bangladesh and Pakistan, which supply domestic helpers to countries such as Bahrain, Lebanon and the United Arab Emirates.

SAN DIEGO — Aethlon Medical, Inc. (OTCBB:AEMD) today announced results of the “first-in-man” study of the Aethlon Hemopurifier® to treat Human Immunodeficiency Virus (HIV), the disease that causes Acquired Immune Deficiency Syndrome (AIDS). In the study, viral load was reduced by 92% in an HIV-infected individual who received a total of twelve Hemopurifier® treatments administered thrice weekly over the span of one month. The study, which was conducted in the absence of any antiviral drug therapy, documented initial viral load of 102,759 iu/ml being reduced to 7,960 iu/ml at the conclusion of the study. The study, which was conducted at the Sigma New Life Hospital in Punjab, India, was designed to provide insight that will define future clinical programs and commercialization pathways for the Aethlon Hemopurifier®.

The Hemopurifier® is a therapeutic filtration device that serves as an artificial adjunct to the immune system. In HIV care the Hemopurifier® targets the clearance of all circulating strains of infectious HIV, including varieties that cause patients to fail antiviral drug regimens. Additionally, the device assists to preserve the immune response through the removal of gp120 and other toxic proteins that shed from HIV to kill-off immune cells, the hallmark of AIDS. Beyond HIV care, the Hemopurifier® is a leading broad-spectrum treatment candidate against drug and vaccine resistant viral pathogens.

“Our first HIV treatment experience supports the vision of our Hemopurifier® becoming a primary strategy to inhibit disease progression once an individual becomes resistant to antiviral drugs,” stated Aethlon Chairman and CEO, Jim Joyce. “Additionally, our device offers a synergistic mechanism of action that could enhance and extend the benefit of both established and candidate antiviral therapies,” concluded Joyce.

According to the World Health Organization, an estimated 33 million people worldwide are infected with HIV, the virus that causes AIDS, and last year 2.2 million people died of AIDS-related illnesses. While there is no cure, HIV antiviral drug regimens have allowed people to live longer with HIV infection. Over time, resistance to these medications can evolve to eliminate the benefit of antiviral drugs, thus leaving infected individuals without further treatment options.

The individual enrolled in the Hemopurifier® study had end stage renal disease (ESRD) and was clinically defined as having AIDS based on a CD4+ T-cell percentage of total lymphocytes of 13.5% at the outset of Hemopurifier® therapy. A percentage below 14% is a defining event that indicates HIV infection has progressed to AIDS. By the end of the Hemopurifier® study, CD4+ T-cell percentage of total lymphocytes increased to 18.09%. Corresponding CD4 lymphocyte counts decreased from 215 cells/µL to 168 cells/µL. Post study follow-on testing indicated that HIV viral load was 57% lower (43,398 iu/ml) than initial study values when measured 14-days after administration of the last Hemopurifier® treatment. The principle investigator of the study reported the patient felt an improved sense of well being, including increased energy and appetite during the study. There were no observed adverse events reported by the principle investigator. All viral load measurements were performed with real-time quantitative polymerase chain reaction (RT-PCR), with treatment samples being measured in duplicate.

Based on previous treatment outcomes in Hepatitis-C (HCV) infected patients, Aethlon management believes the Hemopurifier® to be the first therapeutic candidate to demonstrate meaningful viral load reductions in both HIV and HCV infected individuals. According to the Centers for Disease Control and Infection (CDC), about one quarter of HIV-infected persons are also infected with HCV. HCV is one of the most important causes of chronic liver disease and HCV infection progresses more rapidly to liver damage in HIV-infected persons. HCV infection may also impact the course and management of HIV infection. In addition, HIV suppression of the immune system reduces patient ability to tolerate the HCV standard of care.

Beyond the potential to treat individuals infected with both HIV and HCV, the opportunity for the Hemopurifier® in HCV care is significant, as approximately 170 million people worldwide (3% of the world's population) are HCV infected. According to the World Health Organization (WHO), only 30-50% of infected patients beneficially respond to the 48-week pegylated interferon-ribavirin treatment standard.

In studies of HCV infected individuals, treatment with the Hemopurifier® resulted in robust viral load reductions in HCV patients who completed a treatment protocol of three, 4-hour Hemopurifier® treatments every other day during the course of one week. The study was conducted at the Fortis Hospital in Delhi, India.

European study confirms that HIV treatment within three months of birth improves outcome for HIV-positive infants

HIV infected infants who start HIV treatment within three months of birth have a significantly reduced risk of developing AIDS or dying, European investigators report in the March 13th edition of AIDS. “Deferring treatment in infected infants is no longer an option”, write the investigators.

Without HIV treatment approximately 20% of HIV-infected infants born in richer countries like the UK will develop AIDS or die in the first year of life. The introduction of combination HIV treatment in the mid 1990s lead to suggestions that starting HIV treatment soon after birth could reduce the risk of disease progression in infected children. There were, however, concerns about the pharmacokinetics of antiretroviral drugs in children, the lack of paediatric formulations and the risk of both short- and long-term side-effects.

HIV prevalence is significantly higher amongst men who have sex with men in Laos (Lao People’s Democratic Republic) than any other group in the country, according to a study published in the January 28th edition of AIDS.

The study was conducted in the capital, Vientiane, and found that 6% of men who have sex with men were HIV-positive, and that attempted suicide was associated with HIV infection, a finding that the investigators believe “may point to the mental health needs of men who have sex with men.”

HIV prevalence in Laos is low compared to neighbouring countries such as Cambodia, Thailand and Vietnam. Research has suggested that 0.1% of the adult population in Laos are HIV-positive, and that approximately 1% of female sex workers are infected with HIV.

Half million deaths from cryptococcal meningitis a year in people with HIV

Researchers have estimated that there were about one million infections and a half a million deaths from HIV-related cryptococcal meningitis worldwide in 2006. The findings published in the February 20th edition of the journal AIDS also show that sub-Saharan Africa had the highest global burden of cryptococcal meningitis among people living with HIV.

The scientists (led by Benjamin J. Park of the US Centers for Disease Control) did the study because although although cryptococcal meningitis is one of the most widely reported HIV-related opportunistic infections, the global burden is unknown

In regions with higher HIV burdens, particularly sub-Saharan Africa, cryptococcal meningitis has been reported to be on the increase (more than any other type of meningitis).

Screening for cryptococcal antigens in HIV-positive patients before the initiation of antiretroviral therapy (ART) is a highly effective way of identifying those at risk of developing cryptococcal meningitis, researchers from South Africa have found.

Cryptococcal meningitis is one of the leading causes of death in ART patients who die during the first year of treatment, accounting for up to 20% of all deaths.

The majority of patients at risk of cryptococcal meningitis have detectable Cryptococcus antigen more than three weeks prior to developing meningitis, so a screening test could prevent many cases if patients are then able to receive prompt preventive treatment with the anti-fungal drug fluconazole, or with amphotericin B if a lumbar puncture shows evidence of central nervous system involvement.

On March 10, 2009, FDA granted tentative approval for a generic formulation of lopinavir/ritonavir Tablets, 200 mg/50 mg, manufactured by Matrix Laboratories, Ltd., of Hyderabad, India, for use in combination with other antiretroviral agents for the treatment of HIV-1 infection.

This is a generic formulation of Kaletra Tablets, 200 mg/50 mg made by Abbott Laboratories.

"Tentative approval" means that FDA has concluded that a drug product meets all required quality, safety and efficacy standards, but is not eligible for marketing in the U.S. because of existing patents. Tentative approval, however, does make the product eligible for consideration for purchase outside the United States under the President's Emergency Plan for AIDS Relief (PEPFAR).

Effective patent dates can be found in the agency's publication titled Approved Drug Products with Therapeutic Equivalence Evaluations, also known as the "Orange Book".

This application was reviewed under expedited review provisions developed by FDA for the PEPFAR program

As with all generic applications, FDA conducts an on-site inspection of each manufacturing facility, and of the facilities performing the bioequivalence studies, to evaluate the ability of the manufacturer to produce a quality product and to assess the quality of the bioequivalence data supporting the application prior to granting approval or tentative approval to these applications.

Melbourne, Mar 11 : An Australian scientist has claimed that HIV (Human Immunodeficiency Virus) may adapt so that it is no longer a life-threatening virus.

Speaking ahead of the launch of Adelaide University's Robinson Institute, Roger Short, a professor from Melbourne University's medicine faculty, said it was not in the virus's interest to kill its host.

"If we look into long term future, if humans survive that long, it seems likely that over time the virus, which mutates incredibly rapidly, will eventually adapt so it doesn't kill us," News.com.au quoted Short, as saying.

"Chimpanzees suffer no disease when infected with HIV, whereas for us it is lethal; can we learn from chimpanzees how to protect ourselves?" the expert added.

During the speech, Short urged his fellow researchers to help discover what currently protects sperm and eggs from contracting HIV.

"That is a key question," he said.

"And we need to know more about how gametes (mature reproductive cells) are formed," he added.

According to Short, HIV's evolution could enable the virus to get into reproductive cells - called germ cells - causing it to be passed on to new generations through DNA.

"Geneticists have been able to trace several inserts into our genes which must have come from viruses in the past, hundreds or thousands of years ago," he said.

"Once HIV gets into our sperm it really will have become part of us.

"Maybe some of the research that the (Robinson) institute does on all the stem cells ... will tell us what is so very special about germ cells that protects them from being infected by viruses," he added.

Specialists Are Highly Satisfied With The Safety And Efficacy Of Atripla And Isentress In The Treatment Of HIV Patients

Decision Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, finds that surveyed infectious disease specialists identify a therapy's effect on the ability to achieve viral load suppression in treatment-naive patients as the attribute that most influences their prescribing decisions in HIV. Surveyed specialists indicate they are highly satisfied with Gilead/Bristol Myers Squibb's Atripla and Merck's Isentress in this attribute.

The new report entitled HIV: Opportunity lies for Drug Developers in Integrase Inhibitors and Next Generation CCR5 Antagonists finds that a novel drug in the CCR5 antagonist class that is dosed once daily and achieves maximum physician expectations would earn an 18 percent patient share in HIV in the United States and a 30 percent patient share in Europe, according to surveyed U.S. and European infectious disease specialists.

In 2008, Decision Resources' proprietary clinical gold standard for HIV was Merck's Isentress/Gilead's Truvada. Based on expert opinion, Isentress/Truvada will retain clinical gold standard status through 2017, owing to its balance of efficacy, novel mechanisms of action and safety. Although some therapies in development for HIV hold promise, most have efficacy, safety and tolerability, and/or delivery features that interviewed thought leaders believe are inferior when compared with Isentress/Truvada.

HIV: Opportunity lies for Drug Developers in Integrase Inhibitors and Next Generation CCR5 Antagonists is a DecisionBase 2009 report. DecisionBase 2009 is a decision-support tool that provides in-depth analysis of unmet need, physician expectations of new therapies and commercial dynamics to help pharmaceutical companies optimize their investments in drug development.

The report can be purchased by contacting Decision Resources. Members of the media may request an interview with an analyst.

About Decision Resources

Decision Resources (http://www.decisionresources.com) is a world leader in market research publications, advisory services and consulting designed to help clients shape strategy, allocate resources and master their chosen markets. Decision Resources is a Decision Resources, Inc. company.

Efavirenz dose reduction safe for patients with gene associated with high drug levels and side-effects

Doses of efavirenz (Sustiva) can be safely reduced by up to two-thirds in patients who develop side-effects if these are due to a genetic mutation resulting in high concentrations of the drug, Japanese investigators report in the January 28th edition of AIDS. Furthermore, a Japanese company has developed a low-cost test to see which patients have this mutation.

Efavirenz is metabolised by the liver using the p450 2B6 (CYP2B6) pathway. Earlier research has shown that patients who have a mutation, or polymorphism, in the gene associated with metabolising efavirenz called CYP2B6 516G>T have extremely high blood levels of the drug when treated with the drug’s standard once-daily dose of 600mg.

Japanese investigators performed a study to see if was possible to reduce the dose of efavirenz in patients with this polymorphism who had high concentrations of efavirenz.

Their study involved twelve individuals. Five had their dose of efavirenz reduced to 400mg once daily, the other seven to 200mg daily. Viral load remained undetectable in all twelve individuals.

Nine of the patients had experienced chronic central nervous system side-effects when taking full-dose efavirenz. However, these side-effects improved in nine individuals on reduction of the efavirenz dose.

They highlight the case of a 71-year-old man who had reported virtually nightly nightmares after starting full-dose efavirenz treatment. His blood concentrations of the drug were extremely high and tests revealed that he had the genetic mutation associated with high levels of the drug.

Reduction of his efavirenz dose to 400mg daily resulted in a dramatic improvement in his dreams. His efavirenz concentrations nevertheless remained high and further reduction of the daily dose to 200mg resulted in a complete disappearance of his dreams. Levels of the drug in his blood were within target levels and his viral load was still undetectable two years after the dose of the drug was reduced to 200mg.

Cost had been highlighted as a potential barrier to testing efavirenz-treated patients for the mutation associated with high concentrations of the drug. However, the investigators report that a Japanese company has developed a test costing approximately US$75, “thus, the financial benefits of reducing efavirenz dosage should compensate for the cost of genotyping”, they suggest. However they note “further larger-scale studies are needed to discuss genotype-based tailored efavirenz treatment.”

Studies from Europe and the U.S. Provide Further Information on Sexual Transmission of Hepatitis C Virus among HIV Positive Men

Starting in 2000, clinicians in several large European cities began reporting clusters of apparently sexually transmitted acute hepatitis C virus (HCV) infection, primarily among HIV positive men who have sex with men (MSM). More recently, similar outbreaks have also been reported in the U.S.

In several posters presented at the 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009) last month in Montreal, researchers provided further data on the maturing HIV/HCV epidemics in Europe and the newer outbreaks in the U.S.

Ongoing Epidemic in France

Jade Ghosn and colleagues presented evidence of ongoing sexual transmission of HCV among MSM in France, based on a national survey of acute hepatitis C cases conducted by the French National Institute for Public Health Surveillance in 2006-2007.

The survey included a sample of patients from 115 medical wards across the country, based on the number of HIV and AIDS cases in MSM reported to the National HIV surveillance system. Acute HCV was defined as a positive HCV antibody or HCV RNA within 1 year of a documented negative test.

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"We show evidence for ongoing sexual transmission of HCV in HIV-infected MSM in France, with an ongoing epidemic transmission of genotype 4d virus in the Parisian area," the investigators concluded. "Our results support the need for regular screening for HCV infection in HIV-infected MSM."

Rapid Rise in Amsterdam

Guido Van Den Berk and colleagues reported a rapid rise in acute hepatitis C cases at OLVG Hospital in Amsterdam, which currently cares for more than 1800 HIV positive patients, about three-quarters of them MSM.

The researchers retrospectively reviewed data on HIV positive MSM identified with HCV coinfection between January 2000 and August 2008. Stored blood samples here tested for HCV antibodies and HCV RNA in an attempt to narrow the potential seroconversion interval.

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"Our study confirmed a marked increase in the occurrence of acute HCV starting from 2003 and escalating in 2008, and mostly involving HCV genotypes with a poor response to therapy," the investigators concluded. "In the absence of classical risk factors, HCV has become a sexually transmitted disease in HIV-infected MSM. Efforts to contain this epidemic should be started rapidly."

Risk Factors in New York vs the U.K.

Researchers at Mt. Sinai Hospital and School of Medicine in New York City were among the first to report an outbreak of apparently sexually transmitted HCV among MSM in the U.S.

Sarah Fishman and colleagues undertook an analysis comparing characteristics and risk behaviors among HIV positive men with acute hepatitis C in New York and in the United Kingdom, where the first European cases were reported.

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"HCV transmission among HIV-infected [MSM] is not the result of adolescent risk taking, rather transmission is occurring primarily in men over the age of 35 years," the investigators concluded. "This demographic feature raises the possibility that older age may be a risk factor for sexual transmission of HCV, as previously reported. The greater use of non-injection recreational drugs in the U.K. cases was a notable finding."

Liver Disease Progression

The Mt. Sinai team also presented the latest data on liver disease progression and treatment response in HIV positive individuals with acute HCV infection.

Daniel Fierer first reported at the 2007 CROI that HIV positive MSM with acute hepatitis C showed evidence of unusually rapid and severe liver fibrosis, which typically develops much later in the course of HCV infection. He followed up with similar findings at the 2008 CROI and published further data in the September 1, 2008 issue of the Journal of Infectious Diseases.

As of this report, the investigators had enrolled 45 HIV positive MSM with acute hepatitis C, defined as newly identified HCV antibody seropositivity with either ALT elevation, >1 log HCV viral load fluctuation, or high clinical suspicion. The median age was 40 years, the median CD4 count was 525 cells/mm3, and 94% had HIV viral load < 400 copies/mL; 89% had HCv genotype 1 (this cohort overlaps with the New York group described above).

Just 4 patients (9%) spontaneously cleared HCV infection -- lower than the 25% or so typically seen in studies of HIV negative people with acute hepatitis C. Of the remainder, 15 started hepatitis C therapy, all with pegylated interferon plus ribavirin, while 20 refused or deferred treatment and 6 were still being evaluated.

Of the 10 patients who completed a 24-week post-treatment follow-up period, 8 achieved sustained virological response (SVR) while 2 were non-responders (others are still undergoing treatment).

For 24 participants, liver biopsies were performed a median of 4 months after the first identified ALT elevation. Within this group, 1 patient (4%) had stage 3 fibrosis (using the 0-4 Scheuer scale), 18 (75%) had stage 2, 3 (13%) had stage 1, and 2 (8%) had stage 0.

In a case-control study of 21 matched HCV infected/HCV-uninfected pairs, significant risk factors for HCV infection were unprotected receptive anal intercourse with or without ejaculation (P = 0.03-0.04), unprotected receptive oral sex with ejaculation (P = 0.03), use of sex toys (P = 0.03), sex while high on drugs (P = 0.01), and use of marijuana (P = 0.04). Interestingly, in this analysis getting fisted was not a risk factor, while active fisting was associated with a slightly higher risk that did not reach statistical significance.

"Acquisition of HCV infection in the outbreak of acute HCV infection in HIV-infected MSM in New York City is associated with receptive, unprotected sex and results in early and rapid progression of liver fibrosis," the researchers concluded, confirming their earlier findings.

"Treatment is highly successful when initiated in the acute phase but many do not receive prompt treatment, missing the opportunity to prevent further progression of the already significant liver fibrosis," they continued.

"We therefore recommend at least quarterly ALT and yearly HCV testing for all HIV-infected MSM and rapid referral to an HCV treatment expert upon suspicion of HCV" they added. "Promotion of safe sex and decreased drug use is also warranted."

Screening in 6 U.S. Cities

Finally, Karen Hoover with the Centers for Disease Control and Prevention (CDC) and colleagues estimated the proportion of HIV positive MSM receiving care at 8 HIV clinics who were ever screened for hepatitis A virus (HAV), hepatitis B virus (HBV), or HCV.

HIV management guidelines have consistently recommended that HIV positive individuals should be screened for HBV, which can be prevented with a vaccine if a person is unexposed; there is also a vaccine for HAV, but not for HCV. Despite the mounting evidence that HCV is sexually transmitted among HIV positive MSM, screening is not yet routine.

The present analysis looked at medical record of 1607 patients who made approximately 12,000 visits to 8 clinics in 6 cities (Atlanta, Chicago, Los Angeles, Miami, New York, and San Francisco) since 1998.

The investigators found that while just 45% of the men had been tested for HAV and 48% for HCV, the rate for HBV was much higher, at 89%.

"Screening for HBV and HAV infection and vaccination of susceptible persons are important preventive services in the management of HIV-infected persons," the researchers concluded. "Screening for HBV and HCV infection and evaluation of those persons with chronic infection is important to identify those who require treatment and may be at risk for progressive liver disease."

Most people consume far too much salt, and a University of Iowa researcher has discovered one potential reason we crave it: it might put us in a better mood.

UI psychologist Kim Johnson and colleagues found in their research that when rats are deficient in sodium chloride, common table salt, they shy away from activities they normally enjoy, like drinking a sugary substance or pressing a bar that stimulates a pleasant sensation in their brains.

"Things that normally would be pleasurable for rats didn't elicit the same degree of relish, which leads us to believe that a salt deficit and the craving associated with it can induce one of the key symptoms associated with depression," Johnson said.

The UI researchers can't say it is full-blown depression because several criteria factor into such a diagnosis, but a loss of pleasure in normally pleasing activities is one of the most important features of psychological depression. And, the idea that salt is a natural mood-elevating substance could help explain why we're so tempted to over-ingest it, even though it's known to contribute to high blood pressure, heart disease and other health problems.

Cell phones belonging to hospital staff were found to be tainted with bacteria -- including the drug-resistant MRSA superbug -- and may be a source of hospital-acquired infections, according to study released Friday.

Researchers from the Ondokuz Mayis University in Turkey led by Fatma Ulger tested the phones and dominant hands of 200 doctors and nurses working in hospital operating rooms and intensive care units.

Ninety-five percent of the mobile phones were contaminated with at least one type of bacteria, with the potential to cause illness ranging from minor skin irritations to deadly disease.

Nearly 35 percent carried two types of bacteria, and more than 11 percent carried three or more different species of bugs, the study found.

Most worring, one in eight of the handsets showed methicillin-resistant Staphylococcus aureus (MRSA), a virulent strain that has emerged as a major health threat in hospitals around the world.

Only 10 percent of staff regularly cleaned their phones, even if most followed hygiene guidelines for hand washing, the study noted.

"These mobile phones could act as a reservoir of infection which may facilitate patient-to-patient transmission of bacteria in a hospital setting," the authors warned.

Several strains of drug-resistant bacteria are generally harmless to healthy people but can become lethal to hospital patients in weakened conditions. The bacteria slip into open wounds and through catheters or ventilator tubes, typically causing pneumonia or bloodstream infections.

The researchers noted that more studies were needed to confirm their findings, which were based on a relatively small sampling.

(Vienna , March 11, 2009) - The new UN Political Declaration on Drugs, designed to guide drug policy for the next 10 years, lacks critically important measures for treating and stemming the spread of HIV, Human Rights Watch, the International AIDS Society, and the International Harm Reduction Association said today.

The groups said that respect for human rights and HIV prevention should be at the heart of the policy, but that critical elements had been stripped from the final declaration. They called on member governments to refuse to support the declaration, which is being considered at the high-level segment of the Commission on Narcotic Drugs (CND) this week in Vienna .

"Government delegations could have used this process to take stock of what has failed in the last decade in drug-control efforts, and to craft a new international drug policy that reflects current realities and challenges," said Prof. Gerry Stimson, executive director of the International Harm Reduction Association. "Instead, they produced a declaration that is not only weak - it actually undermines fundamental health and human rights obligations."

What is at issue is a series of measures known collectively as "harm reduction services," which have been endorsed by UN health and drug-control agencies, including the UN Office on Drugs and Crime, UNAIDS and the World Health Organization. These measures include needle and syringe exchange and medication-assisted therapy (for example, with methadone), both inside and outside prisons, as essential to address HIV among people who use drugs. The groups noted that a wealth of evidence proves harm reduction is essential to HIV prevention for people who use drugs. The action was taken against the direct advice of UNAIDS, the Global Fund to fight AIDS, Tuberculosis and Malaria, and the UN special rapporteurs on health and on torture.

Up to 30 percent of all HIV infections outside of sub-Saharan Africa occur via unsafe injecting drug use. The groups said there is clear evidence that harm reduction interventions can halt or even reverse HIV epidemics among people who inject drugs.

"This political declaration fails public health," said Craig McClure, executive director of the International AIDS Society. "Coming less than 12 months after UN member states convened a high level meeting in New York to restate the international commitment to fight HIV, the denial of any reference in the declaration to life-saving harm reduction programs is unacceptable and unconscionable."

In the United States, blacks are disproportionately affected by the HIV/AIDS epidemic. What is being done to curb this crisis?

No one statistic best illustrates the devastating impact of HIV/AIDS on the black population in the United States.

Blacks represent 12% of the population but account for 46% of Americans with HIV/AIDS, according to data from the CDC. Forty-five percent of all new HIV infections in the United States are now among blacks.

The rate of new HIV infections among black men is six times higher than it is for white men and three times higher than it is for Hispanic men. While there are fewer new infections among black women than black men, black women are far more affected by HIV than women of other races. They are 15 times more likely to contract HIV than white women and four times more likely than Hispanic women.

For this article, Infectious Disease News contacted several experts working on this health issue who agree that immediate action is needed. What remains unclear is exactly where that action should be focused.

In the United States, the most dramatic increases in the HIV/AIDS epidemic have been among black men who have sex with men. This fall, the CDC reported that 63% of new HIV infections in black men now occur among MSM. Young black men are especially impacted.

In 2006, there was a higher number of infections among black MSM aged 13 to 29 years than in any other age or racial group of MSM. Most experts cite stigma and homophobia as driving factors behind the heavy burden of HIV in this population.

Lisa Bowleg, PhD, associate professor in the department of community health and prevention at the School of Public Health at Drexel University in Philadelphia, is conducting research on the experiences of ethnic and sexual minorities. “Young black MSM live at the intersection of racism, sexism and homophobia,” she told Infectious Disease News. “When we talk to young men about these three societal pressures, we get a clear picture of a life of unrelenting stress.”

Bowleg said that such stresses can lead to chronic health problems, including obesity and hypertension, and she contends that HIV should be added to that list. She said the lives of many young MSM place them in situations conducive to HIV transmission, often on a daily basis.

Julie Scofield, executive director of the National Alliance of State and Territorial AIDS Directors, echoed this point. “You have issues of being gay and what it means in this country and how to address the needs of gay people,” she said. “Then you are addressing all of those things about being black. When you put those two together it ends up being more than a double whammy. All of this is compounded by issues of stigma and homophobia that exist in black communities. High-risk behaviors often are a natural consequence of such conditions.”

A further complication is self-stigmatization — or internalized stigmatization — that experts like Scofield have observed among black MSM. “We have seen black gay men wonder whether their lives have value,” she said. “The messages they have been raised with in the black community about what it means to be a man often tell them otherwise.”

Victoria Cargill, MD, MSCE, director of Minority Research and Clinical Studies at the Office of AIDS Research at the NIH, discussed this phenomenon. “Young black MSM absorb what they perceive to be the values around them and then use those values to beat themselves,” she said in a recent interview. “Many feel as though they are not living up to the call of being a black male, whatever that might mean.”Identity is an issue

According to Cargill, black MSM who identify themselves primarily as homosexual are more likely to get tested for HIV, to understand HIV/AIDS protection and to be aware of risk behaviors and how to modify those behaviors.

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Social determinants

David Malebranche, MD, MPH, assistant professor at the Emory University Division of General Medicine in Atlanta, discussed the shifting priorities of the fight against HIV/AIDS among black Americans. “I think the biggest challenge is moving our approach away from one that is crisis-mode and disease-first,” he said in an interview. “We need to work backward to an approach that looks at the larger structural and social conditions disproportionately impacting black Americans.” Among those conditions are poverty and inadequate housing, he said.

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Effect of incarceration

“We know now that there is no evidence of widespread HIV transmission in prisons, but because prisons bring together such a high-risk population, it certainly provides a unique opportunity for intervention,” Fenton said. “This incidental point can have an impact not only for the prison itself but outside the walls as well.”

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Intervention by black churches

Cargill said many black churches have taken the issue head-on by providing HIV/AIDS ministries and links to care. Others have simply provided a place for pamphlets in the church vestibule. Others grapple with the realization that the behaviors the church condemns often lead to HIV transmission. The response can vary from neighborhood to neighborhood and from congregation to congregation.

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National strategy

President Barack Obama has emphasized the need for a national strategy to tackle AIDS in the United States, particularly among black Americans. Scofield said that community organizations — both religious and secular — could provide the backbone of a coordinated national strategy.

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Education needed

Education is key to fighting the HIV epidemic, Cargill said. The economic benefits are clear: Education helps people find employment that leads to stable housing and health insurance. Education is also likely to lead to better health-related decisions.

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Role of physicians

Malebranche said that physicians need to do a better job of educating patients. “We all need to be better clinicians and consider the whole patient, not just the patient as disease,” he said.

Clinicians are trained to view the social history of patients in terms of broad, incomplete categories like "smoker" or "drug user." “This puts us in a position where we are working from a deficit model,” Malebranche said. “It does not embrace who our patients are or what their motivations are. Medical schools and residency programs need to develop a much more biopsychosocial model of health care and train people accordingly.”

The physician needs to be aware that the patient is not simply a black man, an injection drug user or an MSM, according to Cargill.

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Public-private partnerships needed

Most researchers believe that the efforts by community-based organizations to raise awareness about the HIV/AIDS epidemic are vital. “The PhDs are not necessarily churning out the best interventions,” Bowleg said. “There are people on the ground level who are really making things happen.”

Public-private partnerships with such organizations are mobilizing and making positive progress. “Leaders within black communities are really beginning to embrace this issue, and we are seeing mainstream institutionalized black organizations focusing on HIV/AIDS as a legitimate crisis,” Scofield said.

Generic drugs could be the next big thing in fighting the AIDS epidemic in the U.S., an HIV clinician told conference attendees in Cabazon today.

“What it means is more drugs for more people,” said Virginia Cafaro, M.D., an HIV clinician and medical director of The WellSpring Medical Group, one of the largest primary care practices in the country.

“Once you start having tolerable drugs and cheap, those are going to become the first lines of medication.”

Most of HIV meds in the U.S. are branded and very expensives costing as much as $1,000 monthly, Cafaro said.

AZT is expected to come out with a generic brand in the next couple of years. Some of the same medications sold in the U.S. are made as generics abroad and can be purchased for about $1.

Hosted by the Riverside Count Department of Public Health, the 5th annual Inland Empire HIV/AIDS conference discussed the epidemic and the need for multi-cultural approaches to educate the public. More than 250 people from various community based organizations serving AIDS patients and healthcare workers attended the conference.

Another emergy therapy that is expected to come on the market in the next couple of years is a gell contraceptive women can use to guard against infection, Cafaro said.

Early prevention is also having a huge impact. Because the HIV virus is drug resistant, traditional wisdom said to put off drug therapy. A guideline change last year encourages earlier treatment following a 2007 UK study that showed patients had fewer side effects.

Worldwide, about 25 million people have been diagnosed with HIV/AIDS since 1990, amid unprecedented educational campaigns and medical research.

“My generation has failed to impart the history of this epidemic,” the Rev. Christoph Sandoval, an AIDS pioneer, said.

“This has been the profanity of the epidemic: cultural competance. The idea of tayloring the messenger and empowering the audience is critical.”

The Inland Empire accounted for nearly 10 percent of those in the state living with HIV/AIDS in 2007, according to data compiled by the San Bernardino County Health Department.

HIV inflection is an issue that is particularly important in the Palm Springs area, which boasts one of the largest gay populations per capita in the United States. Gay and bisexual men of all races account for the majority of those living with HIV.

Riverside County ranks fifth in the state with about 4,200 people infected or living with AIDS.

Each year in California, an estimated 5,000 to 7,000 people become infected. About one in five do not know they are infected.

The conference also included topics on HIV prevention programs for seniors, medical marijuana, Hepatitis C and co-infection.

HIV-1 Can Persist in Aged Memory CD4+ T Lymphocytes With Minimal Signs of Evolution After 8.3 Years of Effective Highly Active Antiretroviral Therapy

During long-term suppressive HAART, HIV is able to persist in terminally differentiated CD4+ T cells as proviral DNA of which the evolution is restricted to a minimum.....One suggested mechanism which could contribute to the latent reservoir is a low level of ongoing viral replication.11,48 Viral replication under selective pressure of HAART will ultimately lead to emergence of drug-resistant viruses. However, no major drug resistance mutations in protease did develop in our patients. Our study thus extends the findings of a previous study reporting a lack of drug resistance development in protease in PBMCs after 2 years of successful HAART by a period of almost 7 years

A Noninferiority Study of Saquinavir/Ritonavir Versus Lopinavir/Ritonavir as Initial HIV-1 Therapy in Adults

The results from the Gemini study demonstrate that SQV/r is noninferior to treatment with LPV/r in efficacy, is similar in tolerability, and results in significantly lower increases in TG values. These data provide further information on therapeutic options for the physician who must weigh the risk factors associated with initial therapy for HIV-1 therapy patients. The results also add further support to the current treatment guidelines that boosted PIs are a viable component of highly active antiretroviral therapy in first-line therapy of HIV-1-infected patients.

Inflammatory Markers among Abacavir and non-Abacavir Recipients in the Womens' Interagency HIV Study and the Multicenter AIDS Cohort Study

Biomarker level changes were seen between the baseline & index visits (D-dimer and IL-6 decreases, hsCRP increases), and were comparable among persons who initiated ABC vs non-ABC containing HAART. From Jules: of note the biomarker levels as seen in graph below were all with normal ranges suggested by presenter in slide.

ABC use was not indepently associated with elevated plasma levels of hsCRP, IL=6 and d-dimer when compared to levls in non-ABC users.

Another Wave of Acquisitions Is Likely as Companies Worry About Their Drug Pipelines and Health-Care Change

Drug makers have begun a frenzied consolidation drive that is redrawing the industry landscape.

Merck & Co.'s $41.1 billion agreement to acquire Schering-Plough Corp., announced Monday, follows Pfizer Inc.'s $68 billion January takeover deal for Wyeth.. Roche Holding AG's seven-month pursuit of Genentech Inc. was also nearing an agreement Monday, according to people familiar with the situation.

The push to consolidate is being driven by the knowledge that the big companies' pipelines aren't producing enough new moneymakers to keep growth going when major products lose patent protection over the next couple of years. As a result, the drug giants are looking to consolidations that will cut costs by combining research and sales efforts and eliminating other overlaps.

What will be left is an industry dominated by behemoths, raising questions about the fates of smaller drug companies, as well as the countless small biotechs hungry for suitors. Even though their labs aren't what they used to be, the major pharmaceutical companies have product lineups that still command fat margins, giving most of them the cash to pursue deals.

"There are too many companies chasing smaller revenue opportunities, so there's got to be a shakeout," says analyst Tim Anderson at Sanford C. Bernstein & Co. "If you've got cash and the value of the companies you want to buy is lower, it's the perfect setup."

Johnson & Johnson seems most likely to be involved in the next wave of consolidation in the drug industry, analysts say.

(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq:GILD) and CV Therapeutics, Inc. (Nasdaq:CVTX) today announced the signing of a definitive agreement pursuant to which Gilead will acquire CV Therapeutics for $20.00 per share in cash through a tender offer and second step merger. CV Therapeutics' Board of Directors has unanimously approved the transaction and has agreed to recommend to its stockholders that they tender their shares pursuant to the tender offer. CV Therapeutics will become a wholly-owned subsidiary of Gilead. The transaction is valued at approximately $1.4 billion and is expected to be dilutive to Gilead's earnings in 2009, neutral to accretive in 2010 and accretive in 2011 and beyond.

CV Therapeutics focuses on the development of small molecule drugs for the treatment of cardiovascular diseases. In 2008, its two marketed products, Ranexa (ranolazine extended-release tablets), indicated for the treatment of chronic angina, and Lexiscan (regadenoson) injection for use as a pharmacologic stress agent in radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress, contributed to total revenues of $154.5 million. CV Therapeutics' pipeline includes multiple product candidates currently being evaluated for the treatment of atrial fibrillation, pulmonary diseases and diabetes..

"The acquisition of CV Therapeutics represents a unique opportunity to complement and strengthen our growing cardiovascular portfolio," said John C. Martin, PhD, Chairman and Chief Executive Officer, Gilead Sciences. "CV Therapeutics' experienced management team has built a portfolio of marketed and investigational products that address significant unmet medical needs, and that represent a strategic fit with Gilead's capabilities and focus. We look forward to working together with the CV Therapeutics team to bring Ranexa to more patients and deliver on the potential of the company's promising pipeline programs."

"Since our company's founding more than 15 years ago, we have been focused on the development of medications to address cardiovascular disease," said Louis Lange, MD, PhD, Chairman and Chief Executive Officer, CV Therapeutics. "Through the dedication and effort of our employees, we have made tremendous progress in changing the practice of cardiology. We are very pleased with the offer Gilead presented, which we believe represents compelling value for our shareholders."

By mixing nanomaterials that act as fuel and oxidizer, researchers have created a combustible nano explosive that can generate shock waves with Mach numbers up to 3.

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The power of these nano explosives could lead to a breakthrough in drug delivery for cancer and HIV, the researchers explain. First, drugs would be administered with a needle as usual, dispersing through the entire body. But then a hand-held device aimed at the tumor would send a pulse into the tumor. The shock waves created by the pulse would make tiny holes in the cells it was aimed at, allowing the drug to enter the tumor cells. Further, the force of the shock waves would push the drugs to those cells within milliseconds.

The researchers have tested the method on animal tissue, and have demonstrated a 99% success rate – almost all of the cells have properly accepted the drugs. Healthy cells, on the other hand, demonstrate much fewer side effects than with conventional treatments such as chemotherapy. As Gangopadhyay explains, the nano explosives have some different characteristics than conventional explosives.

“In conventional explosives, shock waves are generated during detonation,” she says. “In nanothermites, fast propagating chemical reactions can create shock waves without detonation.” Generating shock waves without detonation is the key to this technology, she says

The purpose of the study was to investigate the safety and efficacy of lemon juice and lemon grass (Cymbopogon citratus) in the treatment of oral thrush in HIV/AIDS patients when compared with the control group using gentian violet aqueous solution 0.5%. Oral thrush is a frequent complication of HIV infection.

In the Moretele Hospice, due to financial constraints, the treatment routinely given to patients with oral thrush is either lemon juice directly into the mouth or a lemon grass infusion made from lemon grass (Cymbopogon citratus) grown and dried at the hospice. These two remedies have been found to be very efficacious therefore are used extensively. Gentian violet, the first line medication for oral thrush in South Africa, is not preferred by the primary health clinic patients due to the visible purple stain which leads them to being stigmatized as HIV-positive. Cymbopogon citratus and Citrus limon have known antifungal properties.

Methods

The study design was a randomised controlled trial. Ninety patients were randomly assigned to one of three groups: gentian violet, lemon juice or lemon grass. Inclusion criteria included being HIV-positive with a diagnosis of oral thrush. The study period was 11 days and patients were followed up every second day. International ethical principles were adhered to during the study.

Results

Of the 90 patients, 83 completed the study. In the intention-to-treat analysis, none of the p-values were significant therefore the null hypothesis could not be rejected. In the analysis of the participants who actually completed the trial, the lemon juice showed better results than the gentian violet aqueous solution 0.5% in the treatment of oral thrush in an HIV-positive population (p<0.02). The null hypothesis in terms of the lemon grass and gentian violet could also be rejected on the basis of the Chi-square test and the likelihood ratio test (p<0.05).

Conclusions

Though the patient population was small, the use of lemon juice and lemon grass for the treatment of oral candidiasis in an HIV population was validated by the randomised controlled trial.

In a small pilot study, 30 out of 34 people who had undetectable viral loads on protease inhibitor-based triple therapy were still virally suppressed 48 weeks after switching to a maintenance regimen of atazanavir/ritonavir only. No major protease inhibitor resistance mutations were found in any of the people whose viral load rebounded on the simplified treatment. The findings were published in the Journal of Infectious Diseases in March.

In several studies, Kaletra (lopinavir boosted by ritonavir) has proven surprisingly effective thus far as a maintenance regimen – i.e., at keeping HIV viral load suppressed in people who switch to Kaletra monotherapy after first suppressing their viral loads on a 'standard' combination regimen.

Investigators are now examining other maintenance regimens of ritonavir-boosted protease inhibitors (PIs), such as in this prospective, 48-week, single-arm open-label study of atazanavir/ritonavir (Reyataz/Norvir). This trial enrolled 36 adults who had maintained an HIV viral load below 50 copies/ml for at least 48 weeks on their first antiretroviral regimen – in all cases, a protease inhibitor (PI) plus two nucleoside reverse transcriptase inhibitors (NRTIs). (In fact, most had been suppressed for a considerable time – a median of 6.8 years.)

At study entry, all participants (except three, who were already taking boosted atazanavir) switched from their current PI to 300mg atazanavir plus 100mg ritonavir, once daily. Six weeks after this switch, two had dropped out of the study (one due to a viral load increase to 50 copies/ml); the remaining 34 then discontinued their NRTIs.

The main end point was time to virologic failure, defined as two consecutive HIV RNA measurements = 200 copies/ml. Previously-reported data had shown that 31 out of 34 patients (91%) maintained viral suppression at 24 weeks after the simplification to atazanavir/ritonavir. (This data was presented at the 13th CROI and subsequently published in JAMA).

Now, after 48 weeks, four participants failed by the stated definition: two at 12 weeks after simplifying, one at 20 weeks and one at 28 weeks. A fifth participant had a detectable plasma viral load of 508 copies/ml at the last study visit, unconfirmed by a second measurement.

Counting only the four repeated failures, the probability of virologic success at week 48 was 88%, with a lower one-sided 90% confidence interval [CI] limit of 81%. Counting the fifth participant as a treatment failure, the success rate was 84% (lower 90% CI, 76%). Finally, using a stricter definition of failure (repeated – although not single – HIV RNA measurements of = 50 copies/ml), the success rate was 82% (lower 90% CI, 73%). (None of these figures include the single participant who withdrew due to viral rebound after switching to atazanavir, but before dropping the NRTIs.)

The study also examined blood plasma levels of atazanavir, residual (low-level) viraemia, and drug resistance mutations. No major PI-associated resistance mutations were found by standard population genotyping in any of the five participants with virologic rebound, although several "minor" mutations (I64V and G73S) were identified. In eight virally suppressed participants who received single-copy assay (SCA) viral load testing, there were no significant differences in HIV RNA levels throughout the course of the study; median levels were less than 1.1 copies/ml overall at 48 weeks.

Atazanavir blood plasma concentrations were measured monthly, and were linked to likelihood of treatment failure. Three participants had undetectable atazanavir concentrations at least once during the study. Two of these three (67%) went on to virologic failure, which occurred in only in two of the 31 (6%) who had consistently detectable atazanavir levels, "strongly suggest[ing] that suboptimal adherence was an important factor in the development of virologic failure." Median plasma concentrations of atazanavir were also lower, although not statistically significantly, in participants with virologic failure (380 ng/ml vs 660 ng/ml, p=.18).

While noting that this was a non-randomised pilot study of patients with a very stable treatment history, the researchers concluded that it "adds to a growing body of data that simplified maintenance therapy with a boosted PI alone is effective in maintaining virologic control after initial suppression with a 3-drug regimen." Adherence and adequate drug concentrations may be particularly important in the continued success of such simplified treatments.

Gastrointestinal Tolerance of the New Tablet Formulation of Lopinavir/Ritonavir (Kaletra)

Boosted protease inhibitors (PIs) are one of the most frequently-used components of combination antiretroviral therapy. One of the first to be widely used was lopinavir/ritonavir (Kaletra), which combines a PI plus a boosting dose of ritonavir in the same pill -- originally a soft-gel capsule followed more recently by a tablet formulation.

The objective of the present study, published in the March 2009 issue of the Journal of Acquired Immune Deficiency Syndromes, was to determine the difference in adverse gastrointestinal (GI) side effects in patients who switched from lopinavir-ritonavir soft-gel capsules to film-coated tablets.

The effectiveness of lopinavir/ritonavir has been widely demonstrated [1,2], the study authors noted as background, and it is currently one of the PIs used as first-line therapy for HIV patients [3,4].

The most commonly reported side effect associated with lopinavir/ritonavir is mild to moderate diarrhea. Nausea and vomiting, changes in blood lipid levels, elevated transaminase (ALT and AST) levels and altered glycemia profiles also have been widely reported. In the Phase 2/3 studies that supported the drug's approval, the drop-out rate due to adverse side effects was 4.5% among treatment-naive individuals and 9% among treatment-experienced patients over 48 weeks [5].

The original soft-gel capsule formulation of lopinavir/ritonavir contained 133.3 mg of lopinavir and 33.3 mg of ritonavir. In addition to GI side effects, lopinavir/ritonavir capsule had low bioavailability when taken without fatty foods, and it was necessary to keep the capsules refrigerated at 4-8 degrees Centigrade in order for the drug to maintain its effectiveness.

With the aid of new technology, it became possible to manufacture a new formulation, a solid-state dispersion of lopinavir/ritonavir in a film-coated tablet containing 200 mg of lopinavir and 50 mg of ritonavir.

The change in formulation created several advantages over the original capsule. These include reduction of the dose from 3 to 2 pills every 12 hours, and the ability to store the drug at room temperature -- a considerable benefit in resource-limited settings. In addition, the absorption rate of the tablets enables use of the drug with or without food [6,7].

Because the rate of adherence to therapy is closely related to the presence of side effects, it is widely accepted that many patients will stop treatment to avoid such adverse events, regardless of the clinical effectiveness of treatment [5].

Preliminary studies suggested that the new lopinavir/ritonavir tablet formulation could cut down the rate of adverse GI symptoms associated with the soft-gel capsules. However, no long-term studies had compared the 2 formulations. (This may no longer be possible, as production and marketing of the soft-gel capsule has been halted.)In the present study, the researchers conducted an uncontrolled, open-label, prospective study that including a pre/post comparison using the Gastrointestinal Symptom Rating Scale (GSRS) modified for the characteristics of HIV PIs.

Results

* 70 patients were included, with a mean treatment time on the new formulation of 77 days. * The total GSRS score was 26.96 in the pre-switch survey and 26.27 in the post-switch survey, with a mean difference of 0.69 points (P = 0.47, not a statistically significant difference). * None of the survey questions reached the objective of a difference of at least 2 points, previously set as a clinically significant difference. * Only 1 patient dropped out of the study due to gastrointestinal symptoms.

In conclusion, the authors wrote, "Our study has unearthed no clinically significant differences in the gastrointestinal tolerance profile of lopinavir/ritonavir soft-gel capsules and lopinavir/ritonavir film-coated tablets, measuring this tolerance level by application of the GSRS scale."

The authors observed that there is only 1 prior study [8] that has provided information about the side effects of the new lopinavir/ritonavir formulation, an open Phase 1 study "in which the main aim is to show the pharmacokinetic bioequivalence between both formulations and to quantify gastrointestinal toxicity on the basis of the notified side effects."

Further, they noted, "From the total of 15 patients included [in that study], 4 report diarrhea in the lopinavir/ritonavir soft-gel capsule group and 2 in the lopinavir/ritonavir film-coated tablet group, with 2 patients reporting abdominal pain in both groups. This same research group published results from the extension of this study, with a total of 63 patients, again recording no differences in the side effects profile of the 2 formulations [6].

The authors of the present study emphasized that monitoring the side effects of antiretroviral therapy "should be considered as a key aspect, especially those symptoms impinging on the patients' quality of life, due to their influence on adherence and ipso facto on therapy effectiveness."

"The contribution of the current study," they wrote, "is the use of a specifically designed tool for monitoring side effects of this type, duly modified by us to bring it into line with the gastrointestinal tolerance profile of the PIs. We believe that this could be a useful tool for monitoring the adverse gastrointestinal symptoms of HIV patients."

WHO and International Researchers Publish Updated List of HIV Drug Resistance Mutations

Emergence of drug resistance is one of the major barriers to long-term effectiveness of antiretroviral therapy. When drugs are used alone, or with other drugs that are no longer active, HIV can develop mutations that allow it to replicate despite treatment. Some people are infected with HIV that already carries resistance mutations even though they have never received treatment (known as primary resistance).

Clinicians test whether an individual has resistant virus in 2 ways: phenotypic tests expose HIV to a drug in the laboratory to see how well the agent inhibits viral replication, while genotypic tests analyze the genome of an HIV isolate to see if it carries mutations known to be associated with resistance.

In the March 6, 2009 edition of the open-access online journal PLoS ONE, Diane Bennett from the World Health Organization (WHO) and colleagues from several international HIV/AIDS research institutions published an updated list of known resistance mutations.

"Programs that monitor local, national, and regional levels of transmitted HIV drug resistance inform treatment guidelines and provide feedback on the success of HIV-1 treatment and prevention programs," they wrote. "To accurately compare transmitted drug resistance rates across geographic regions and times, the World Health Organization has recommended the adoption of a consensus genotypic definition of transmitted HIV-1 drug resistance."

In January 2007, WHO outlined criteria for developing a list of mutations for drug-resistance surveillance and compiled a list of 80 reverse transcriptase (RT) and protease mutations meeting these criteria. Since then, several novel antiretroviral drugs have been approved and several new drug-resistance mutations have been identified.

Elevated Rate of Heart Attacks and Strokes in HIV Patients on HAART Begins to Decline at California Kaiser Permanente

As HIV positive people began to live longer thanks to the development of effective antiretroviral therapy, cardiovascular disease became a growing concern, especially given evidence that HIV infection itself and the drugs used to treat it can increase cardiovascular risk.

However, according to a Kaiser Permanente study presented at the 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009) last month in Montreal, elevated rates of heart attacks and other cardiovascular events among HIV positive patients appear to be declining, and may be approaching those of HIV negative individuals.

Daniel Klein and colleagues identified HIV positive adult members of the Kaiser Permanente California health system -- which cares for more than 6 million patients in California -- matching them 10:1 with HIV negative members of the same age, sex, and year of enrollment in the cohort.

Overall, they analyzed data from 20,305 HIV positive and 203,500 HIV negative participants, contributing 89,683 and 1,063,567 person-years (PY) of follow-up data, respectively. Almost all (90%) were men, the average age was 41 years, and the HIV positive group included a slightly larger percentage of white patients (56%) than the HIV negative group (47%).

"Rates of MI and stroke in a matched sample of HIV negative patients were significantly lower than among HIV positive patients," the investigators stated.

However, they continued, "during 1996-2008, the rates of MI among HIV positive and HIV negative patients converged such that in 2006-2008 the difference in rates between the two groups became statistically non-significant."

"The convergence was due to a decline in the rate of MI among HIV positive patients while the rate among HIV negative patients was stable," they added.

With regard to strokes, they stated, "We observed the same convergence in stroke rates. However for stroke, the convergence was due to a rise in the rate of stroke among HIV negative patients while the rate among HIV positive patients was stable."

Explaining their findings, the investigators concluded, "Among HIV positive patients, the observed decline in rate of MI and stable rate of stroke is consistent with 1) a shift to more lipid friendly antiretroviral retroviral regimens, 2) increased use of lipid-lowering therapy, and 3) effective management of traditional cardiovascular risk factors as evidenced by stable Framingham risk scores despite an aging population."

HIV positive patients taking antiretroviral therapy may experience an array of metabolic complications including lipodystrophy (body fat changes) and altered blood lipid profiles. But research has produced conflicting data about whether these problems are due to HIV infection itself, specific antiretroviral medications, or perhaps a combination of known and unknown factors.

While the thymidine analog NRTIs (stavudine [d4T, Zerit] and zidovudine [AZT, Retrovir]), the "d-drugs" (stavudine and didanosine [ddI, Videx]), and protease inhibitors have most often been linked to metabolic manifestations, the non-nucleoside reverse transcriptase inhibitor [NNRTI] class was thought to have fewer metabolic side effects.

But the NNRTI efavirenz (Sustiva) may cause alterations in lipid metabolism that lead to fat accumulation in the liver (steatosis), according to a poster presented at the 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009) last month in Montreal.

Juan Esplugues from the University of Valencia in Spain and colleagues analyzed molecular mechanisms that might be implicated in alterations of lipid metabolism associated with efavirenz, as well as the role of the so-called "master switch" of regulation of cellular bioenergetics, AMP-activated protein kinase (AMPk).

In this laboratory study, non-infected Hep3B cells (a liver cell line) were stained with a fluorescent probe after 24-hour exposure to efavirenz (10, 25, or 50 mcM). In order to characterize the nature of accumulated lipids, cells were treated for 4 hours with efavirenz (10 and 25 mcM) and intracellular lipid content was determined using nuclear magnetic resonance. In addition, expression of the fatty acid transporters CD36 and FATP was analyzed using a polymerase chain reaction assay. Selected experiments were performed in cells pretreated for 30 minutes with an AMPk inhibitor known as Compound C.

Results

* Efavirenz induced neutral lipid accumulation in hepatic cells after 24-hour incubation (124-147 mcM with efavirenz vs 106 mcM in unexposed control cells). * In the nuclear magnetic resonance experiments, the effects of efavirenz were significant following 4-hour incubation. * The observed profile of the accumulated lipids suggested that they did not originate in the cell membranes. * Changes in lipid accumulation related to efavirenz were not observed when fatty acids were removed from the culture medium, demonstrating that these changes were due to fatty acid uptake from the surrounding extracellular material. * Likewise, changes in lipid accumulation did not occur in the presence of Compound C, suggesting that AMPk plays a key role in this lipid uptake. * The role of AMPk was also underlined by the fact that efavirenz was associated with increased expression of CD36 and FATP mRNA, 2 of the enzyme's downstream targets.

"Our results demonstrate that efavirenz increases fatty acid uptake in hepatic cells, leading to the accumulation of lipids," the investigators concluded. "These lipids have the same chemical composition as those that form droplets."

"Given the long-term treatment of patients with efavirenz, such effects on lipid content suggest that this drug exerts a pro-steatotic role in the liver and could alter lipid metabolism in this organ," they continued. "Due to the importance of the liver in the general regulation of lipids, efavirenz may also be implicated in some of the alterations that are characteristic of lipodystrophy."

NEW DELHI -- People are forgetting to practice safe sex because they no longer fear dying from HIV/AIDS, says the doctor who won the Nobel prize for helping to discover the virus.

Treatment advances mean “some people in my country, France, and other Western countries have become complacent — they see HIV/AIDS as a chronic disease — not as one that can kill,” virologist Francoise Barre-Sinoussi said.

The doctor shared the Nobel Prize last year with fellow French virologist Dr Luc Montagnier for their discovery in 1981 of the human immunodeficiency virus (HIV) that causes AIDS.

Barre-Sinoussi noted there has been a huge leap forward in treatments for HIV/AIDS with a cocktail of drugs that reduces the level of virus in the body and likewise lowers the risk of passing on the pathogen to others.

But she told AFP she worried that people's confidence in retroviral drugs had created a false sense of security, leading to an increase in unprotected sex.

Speaking on the sidelines of a medical conference last week organized by French charity Foundation Merieux in New Delhi, she noted a “frightening” rate of new male-to-male infection in some Western countries such as France.

“We should tell the truth about HIV/AIDS — that new treatments can be very effective, helping them live years longer,” said Barre-Sinoussi.

But she added that HIV/AIDS patients are prone to other illnesses, especially cancers. They can also be resistant to the life-saving drugs, creating “major complications.”

Between 2001 and 2006, male-to-male sex was the largest HIV transmission category in the United States and the only one associated with an increasing number of HIV/AIDS diagnoses, according to the US Centers for Disease Control and Prevention.

About 56,300 people were infected with HIV in the United States in 2006, according to the organization, with gay and bisexual men accounting for about half of all new infections.

For 25 years, researchers have tried and failed to develop an HIV vaccine, primarily by focusing on a small number of engineered "super antibodies" to fend off the virus before it takes hold. So far, these magic bullet antibodies have proved impossible to produce in people. Now, in research to be published March 15 online by Nature, scientists at The Rockefeller University have laid out a new approach. They have identified a diverse team of antibodies in "slow-progressing" HIV patients whose coordinated pack hunting knocks down the virus just as well as their super-antibody cousins fighting solo. By showcasing the dynamic, natural immune response in these exceptional patients, the research, led by Michel C. Nussenzweig, Sherman Fairchild Professor and head of the Laboratory of Molecular Immunology, suggests that an effective HIV vaccine may come from a shotgun approach using of a wide range of natural antibodies rather than an engineered magic bullet.

"We wanted to try something different, so we tried to reproduce what's in the patient. And what's in the patient is many different antibodies that individually have limited neutralizing abilities but together are quite powerful," says Nussenzweig, who also is a Howard Hughes Medical Institute investigator. "This should make people think about what an effective vaccine should look like."

HIV strains mutate rapidly, making them especially wily adversaries of the immune system. But one element is shared almost universally among the diverging strains — a protein on the envelope of the virus called gp140 that HIV needs to infect immune cells. Prior research has shown that four randomly engineered antibodies that block the activity of that protein prevent the virus from infecting immune cells in culture, but all attempts to coax the human body into producing those four have failed.

So Johannes Scheid, a visiting student in Nussenzweig's lab who is now a doctoral candidate, turned his attention to the antibodies produced by six people infected with HIV whose immune systems put up an exceptionally strong fight. The patients represent the roughly 10 to 20 percent of HIV patients who are able to control the virus and are very slow to progress to disease. Their immune systems' memory B cells produce high levels of antivirus antibodies, but until now, researchers have known little about the antibodies or how effective they are.

With help from Rockefeller's Center for Clinical and Translational Science and Rockefeller scientists David D. Ho and Jeffrey V. Ravetch, Scheid and colleagues isolated 433 antibodies from these individuals' blood serum that specifically targeted the envelope protein — the chink in HIV's protean armor. He cloned the antibodies and produced them in bulk, mapped which part of the envelope protein each targeted, and gauged how effective each was in neutralizing the virus. In the process, he identified a new structure within the envelope protein — called the gp120 core — that had never been recognized as a potential target for antibodies. "It's the first time that anyone has defined what is really happening in the B cell response in these patients," says Scheid.

Scheid's work shows that it's common for these antibodies to have neutralizing activity, says Nussenzweig. But each antibody alone has limited ability to fight the virus. "Individually, they're not as strong as the Famous Four," says Nussenzweig, referring to the high-profile super antibodies on which several vaccine attempts have been based. But in high concentrations, a combination of the sets of antibodies cloned from the individual patients seemed to act as teams to knock down the virus in cell culture as well as any single antibody studied to date. These natural antibodies were also able to recognize a range of HIV strains, indicating that their diversity may be an advantage over a single super antibody that focuses on only one part of the virus, which can mutate. The findings suggest that research into vaccines that mimic this natural antibody response could pay off.

The U.S. Food and Drug Administration yesterday approved the first DNA test that identifies the two types of human papillomavirus (HPV) that cause the majority of cervical cancers among women in the United States.

A positive Cervista 16/18 test result indicates whether HPV type 16, 18 or both types are present in the cervical sample.

The FDA also approved yesterday the Cervista HPV HR test, which is the second DNA test that detects essentially all of the high-risk HPV types in cervical cell samples. The Cervista HPV HR test uses a method similar to the Cervista HPV 16/18 test to detect the DNA sequences of these HPV types.

In women age 30 and older or women with borderline cytology, the Cervista HPV 16/18 test can be used together with cytology and the Cervista HPV HR test to assess risk of cervical disease.

“Results from these two tests, when considered with a physician’s assessment of the patient’s history, other risk factors, and professional guidelines, can help physicians better determine risk and could lead to better patient management,” said Daniel G. Schultz, M.D., director of the FDA’s Center for Devices and Radiological Health.

HPV is the most common sexually transmitted infection in the United States. The U.S. Centers for Disease Control and Prevention estimates that more than 6 million Americans become infected with genital HPV each year and that more than half of all sexually active women and men become infected at some time in their lives.

For most women, the body's own defense system clears the virus and infected women do not develop related health problems. However, some HPV types can cause cell abnormalities on the lining of the cervix that later can become malignant. While there are many different types of HPV, types 16 and 18 cause about 70 percent of all cervical cancers.

At least 3 percent of District residents have HIV or AIDS, a total that far surpasses the 1 percent threshold that constitutes a "generalized and severe" epidemic, according to a report scheduled to be released by health officials tomorrow.

That translates into 2,984 residents per every 100,000 over the age of 12 -- or 15,120 -- according to the 2008 epidemiology report by the District's HIV/AIDS office.

"Our rates are higher than West Africa," said Shannon L. Hader, director of the District's HIV/AIDS Administration, who once led the Federal Centers for Disease Control and Prevention's work in Zimbabwe. "They're on par with Uganda and some parts of Kenya."

"We have every mode of transmission" -- men having sex with men, heterosexual and injected drug use -- "going up, all on the rise, and we have to deal with them," Hader said.

In addition to the epidemiology report, the city is also releasing a study on heterosexual behavior tomorrow. That report, funded by the CDC, was conducted by the George Washington University School of Health and Health Services.

Among its findings: Almost half of those who had connections to the parts of the city with the highest AIDS prevalence and poverty rates said they had overlapping sexual partners within the past 12 months, three in five said they were aware of their own HIV status, and three in 10 said they had used a condom the last time they had sex.

We found that 53% of men with undetectable plasma viral loads had measurable virus in their semen

the majority of HIV transmission risk behavior in our sample occurred among men who had the highest concentration of HIV in their semen. It is noteworthy that differences in sexual activity between men with higher and relatively lower concentrations of HIV in semen were significant only for insertive sexual acts. One factor that may explain these findings was the potential co-occurrence of other STIs.

The association of higher rates of insertive intercourse and semen viral loads may therefore be a function of asymptomatic or subclinical urethritis

We recommend that future research investigating relationships between sexual transmission risk behavior and semen viral loads perform more comprehensive clinical examinations for clinical and subclinical urethritis and conduct more comprehensive testing for STIs on larger samples. We also recommend that HIV-positive men be warned that they cannot infer their infectiousness from their plasma viral load test results and that behavioral risk reduction practices remain the only means for preventing the spread of HIV.

Analyses of sexual transmission risk behaviors showed that men with greater concentrations of HIV in their semen relative to concentrations of HIV in plasma reported significantly greater rates of unprotected vaginal intercourse and total number of unprotected sexual intercourse occasions as the insertive partner than men with equal to or greater concentrations of virus in their plasma than semen.

We were particularly interested in patterns of transmission risk behaviors exhibited by men who were more infectious than implicated by their plasma viral load. Given that greater concentrations of virus are typically detected in plasma relative to serum,12 and the demonstrated association between urethritis and viral load in semen,17 we hypothesized that men who presented higher viral loads in semen than blood would be more likely to have a recent STI and would exhibit higher rates of HIV transmission risk behaviors than men whose plasma viral load was equal to or less than their semen viral load.

A sticky business -- how cancer cells become more 'gloopy' as they die

The viscosity, or 'gloopiness', of different parts of cancer cells increases dramatically when they are blasted with light-activated cancer drugs, according to new images that provide fundamental insights into how cancer cells die, published in Nature Chemistry today.

Approximately 8,000 UK residents, 500 from Northern Ireland, were polled and it's now critically apparent that performing safe sex is unequivocally low on our agendas.

Embarrassment at purchasing condoms is a serious matter as it precipitates risk-taking behaviours.

The results from this comprehensive survey indicate that this fear has contributed to the reported doubling of HIV incidents within Northern Ireland from 2007-2008.

Studies have also shown that between 2002-2006, there were dramatic increases in chlamydia, which rose by 51 per cent, gonorrhoea by 11 per cent, genital warts by 17 per cent, and syphilis, which increased by an |astounding 139 per cent.

WASHINGTON--(BUSINESS WIRE)--Biotechnology Industry Organization (BIO) President and CEO Jim Greenwood released the following statement today commending President Barack Obama for his nomination of Dr. Margaret Hamburg as Commissioner and appointment of Dr. Joshua Sharfstein as Deputy Commissioner of the Food and Drug Administration (FDA):

“BIO welcomes the nomination of Dr. Hamburg as the next FDA Commissioner and we urge the Senate to move swiftly to confirm her. The vital work of the FDA touches every American in very personal ways – from ensuring the safety of the foods we serve our families to overseeing the medicines we give our children when they are sick. The FDA needs a strong, confirmed Commissioner to effectively fulfill its expanding obligations, advocate for sufficient agency resources, ensure the integrity of scientific decisions and promote morale and a sense of mission at the agency.

“Dr. Hamburg’s strong background in public health and bioterrorism make her uniquely qualified for this important position. She served as health commissioner for New York City where she implemented several innovative public health programs, including a control program that reduced New York’s tuberculosis rate by 46 percent She has an understanding of the federal health infrastructure, having worked as an AIDS researcher at the National Institutes of Health and later as an Assistant Secretary at the Department of Health and Human Services. Dr. Hamburg also has served as a key member of the Nuclear Threat Initiative, a non-profit organization focused on reducing the public safety threat from chemical, biological and nuclear weapons.

“BIO also welcomes the appointment of Dr. Joshua Sharfstein as Deputy Commissioner as he brings an impressive resume to the FDA as well. A Harvard-trained doctor, he has served as Health Commissioner of Baltimore, Maryland for the past four years. Dr. Sharfstein understands the legislative process well, having served on the professional Committee staff of U.S. Representative Henry Waxman (D-CA).

“Our member companies recognize that a reliable, science-driven regulatory environment fosters innovation, promotes economic competitiveness, and maintains high patient and consumer confidence in the products that FDA regulates. Changes in the world are affecting the health and well-being of every American and the safety of the food that we eat and the drugs, biologics, and medical devices upon which we depend. We welcome the nomination of an FDA Commissioner who can help the agency address the myriad challenges of the 21st century.

“The next FDA Commissioner will play a pivotal role in strengthening the FDA’s ability to operate a modern, scientifically-based agency and ensuring that the agency is fully resourced and prepared to confront future challenges. We appreciate the fact that the Administration has made the swift identification of a FDA Commissioner a priority. The American public deserves such steady, capable and visionary leadership.

“We look forward to working with the next Commissioner, her leadership team and the Congress to ensure that the FDA has the resources necessary to protect America’s patients and consumers.”

Many scientists believe a vaccine that prevents HIV infection will need to stimulate the body to make neutralizing antibodies, infection-fighting proteins that prevent HIV from entering immune cells. Previous research has shown that some individuals who control HIV infection without medication naturally produce antibodies able to neutralize diverse strains of HIV.

Until now, however, scientists were hampered in studying the way effective HIV-neutralizing antibodies arise during natural HIV infection because scientists lacked the tools to obtain more than a few HIV-specific antibodies from any given individual.

A new research endeavor has assembled a group of state-of-the-art techniques for the first time to study the phenomenon of natural antibody-mediated HIV neutralization. The project demonstrates how this system can isolate dozens of HIV-specific antibodies from a single HIV-infected individual, something never accomplished before. Applied prospectively to a large group of HIV-infected individuals, the system will enable scientists to identify and define the diverse set of neutralizing antibodies that arise during natural HIV infection, information that may prove important in vaccine development.

John R. Mascola, M.D., Richard T. Wyatt, Ph.D., and Mark Connors, M.D., all of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, participated in the research, which NIAID co-funded. Michel C. Nussenzweig, M.D., Ph.D., of The Rockefeller University led the team of 22 co-investigators in this collaboration.

The process begins with collecting memory B cells, which produce antibodies, from HIV-infected individuals previously screened for strong neutralizing antibody responses. These B cells are incubated with a specially flagged protein from the outer shell of an HIV virus particle. The HIV-specific memory B cells bind to the flagged protein, enabling researchers to identify these cells, isolate and store them. Then, for each of the HIV-specific memory B cells, a pioneering technique expresses the genes that code for HIV-specific antibodies. Finally, assays help scientists determine which of these antibodies can effectively neutralize HIV.

HAART (highly active anti-retroviral therapy) has emerged as an extremely effective HIV treatment that keeps virus levels almost undetectable; however, HAART can never truly eradicate the virus as some HIV always remains dormant in cells. But, a chemical called suberoylanilide hydroxamic acid (SAHA), recently approved as a leukemia drug, has now been shown to 'turn on' latent HIV, making it an attractive candidate to weed out the hidden virus that HAART misses.

Matija Peterlin at UCSF and colleagues had previously identified another chemical called HMBA that could activate latent HIV, but the risk of several toxic side effects made HMBA clinically non-viable. However, the chemically similar SAHA had received FDA approval, making it a potentially safer alternate.

So, the researchers examined whether SAHA had any effect on HIV latency. They found that SAHA could indeed stimulate latent HIV to begin replicating, which exposes the infected cell to HAART drugs. SAHA could activate HIV in both laboratory cells as well as from blood samples taken from HIV patients on antiretroviral therapy. Importantly, this successful activation was achieved using clinical doses of SAHA, suggesting toxicity will not be a problem.

This study appeared in the March 13 issue of Journal of Biological Chemistry

Ultraviolet lights could reduce the spread of tuberculosis in hospital wards and waiting rooms by 70%, according to a new study, published in PLoS Medicine today. The study, which explored the transmission of tuberculosis (TB) from infected patients to guinea pigs, suggests that installing simple ultraviolet C (UVC) lights in hospitals could help reduce the transmission of TB, including drug-resistant strains.

Every year, over nine million people are infected with tuberculosis and nearly two million people die from the disease, according to the World Health Organisation. Infection rates are particularly high in places where vulnerable people are crowded together, such as hospitals, homeless shelters and prisons.

When a tuberculosis patient coughs, bacteria are sprayed into the air in tiny droplets, floating around the room and infecting other patients, visitors and healthcare staff. These bacteria can be killed by hanging a shielded UVC light from the ceiling with a fan to mix the air, say the researchers, from Imperial College London, the University of Leeds, Hospital Nacional Dos de Mayo, Lima, Perú and other international institutions.

UVC light kills tuberculosis bacteria, including drug-resistant strains, by damaging their DNA so they cannot infect people, grow or divide. It is already used at high intensity to disinfect empty ambulances and operating theatres.

Dr Rod Escombe, the study's principal investigator from the Wellcome Trust Centre for Clinical Tropical Medicine at Imperial College London, said: "When people are crowded together in a hospital waiting room, it may take just one cough to infect several vulnerable patients. Our previous research showed that opening windows in a room is a simple way to reduce the risk of tuberculosis transmission, but this is climate-dependent – you can't open the windows in the intensive care ward of a Siberian hospital for example."

"Thankfully, the rate of tuberculosis infection in countries like the UK is relatively low and people who are infected can be treated using antibiotics, which are readily available here. People are more likely to die from the disease in developing countries like Perú, because there are limited resources for isolating patients, diagnosing them quickly and starting effective treatment. Also, the prevalence of drug-resistant TB is much higher in the developing world. Preventing infection is much easier and cheaper than treating a patient with tuberculosis," added Dr Escombe.

Plans are already underway to install upper room UV lights in the chest clinic at St Mary's Hospital, part of the Imperial College Healthcare NHS Trust, which will be the first hospital to have them in the UK.

Introducing UVC lights could be a relatively low-cost measure, say the researchers. Currently, a typical UVC ceiling light costs around US$350 and replacement bulbs cost from US$25. The researchers are now working to develop more affordable US$100 units.

The impact of UV lights is greatest when combined with careful management of the air flow on the wards, as Dr Cath Noakes from the University of Leeds' Faculty of Engineering explains: "The lights must be set high enough to ensure patients and health workers are not overexposed, but if the lights only treat air at that level, there will be little benefit. To be most effective, ventilation systems need to create a constant flow of treated air down to patient level, and potentially infected air up towards the lights."

To reach their conclusions, scientists hung UVC lights in a hospital ward in Lima, Perú where 69 patients with HIV and TB were being treated. The researchers pumped air from the ward up to a guinea pig enclosure on the roof of the hospital for 535 consecutive days. The guinea pigs were split into three groups of approximately 150: the first group received air exposed to the UV lights in the ward, the second group received ward air treated with negative ionisers, and the third control group was given untreated air straight from the ward. The guinea pigs were given skin tests for tuberculosis once a month.

By the end of the experiment, 35% of the control group were infected with TB, compared to 14% of the ionised air group and 9.5% of the UVC group. 8.6% of the control group developed the active form of the disease after being infected with TB, compared to 4.3% of the ionised air group and 3.6% of the UVC group.

This research was funded by the Wellcome Trust, Sir Halley Stewart Trust and the Sir Samuel Scott of Yews Trust, Proyecto Vigia (USAID) and the charity Innovation for Health and Development (IFHAD).

CD4+ T cell depletion by HIV is a major blow to the immune system. Combination antiretroviral therapy (c-ART) restores the T cell population, however not all patients respond to this therapy.

University of Paris researchers report that administration of interleukin-7 (IL-7) to c-ART--treated, HIV-infected patients with low T cell counts, boosted T cell numbers and was well tolerated for 48 weeks. HIV-infected patients may benefit from intermittent IL-7 therapy in combination with c-ART.

White blood cells known as CD4+ T cells are the main target of HIV. The virus hijacks these cells and replicates within them, which ultimately destroys the cell. This depletion of the T cell population represents a major blow to the immune system and puts HIV-infected individuals at increased risk of opportunistic infections. Treatment of HIV-infected individuals with a cocktail of drugs called combination antiretroviral therapy (c-ART) is able to restore the T cell population and help fight HIV infection, however not all patients respond to this therapy. The growth factor interleukin-7 (IL-7) is known to stimulate T cell production and survival, suggesting that IL-7 may help restore the T cell population during HIV infection.

In a new study published in the JCI, Yves Levy and colleagues at the University of Paris undertook a clinical trial to evaluate the safety and efficacy of repeated IL-7 therapy over a 16-day period in 13 c-ART–treated, HIV-infected patients that possessed low T cell counts despite successful suppression of virus levels with c-ART. In these individuals, IL-7 was well tolerated and boosted the number of CD4+ and CD8+ T cells, which were able to mount an immune response against HIV. These effects were observed for 48 weeks. The data suggest that HIV-infected patients may benefit from intermittent therapy with IL-7 in combination with c-ART.

A study published in the April st edition of Clinical Infectious Diseases reports moderate drug resistance rates in a large Swiss cohort, while also cautioning that resistance data may be misleading if the treatment history of the population of interest is not taken into account. The cohort’s resistance level in 2007 was estimated to be 37% to 45%, much less than what has been reported in some other studies.

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The Swiss HIV Cohort Study was the source of data for the recently reported findings. Researchers analysed data from 8064 antiretroviral-experienced men and women who had been examined at least once between 1999 and 2007. Cohort members were divided into three subgroups: those thought to be at high risk for resistance mutations because they had either taken weak early antiretroviral regimens or had experienced treatment failure; those thought to be at low risk because they were not undergoing treatment or had maintained viral suppression while on treatment; and those whose status was unknown. Most people in the high-risk group had initially been treated with one or two nucleoside reverse transcriptase inhibitors.

About 40% of the study population had undergone HIV genotypic resistance testing. Tests were categorised according to whether people had been in the high-risk subgroup, low-risk subgroup, or unknown subgroup when the sampling occurred. Researchers calculated the proportion of tests in each subgroup that indicated the presence of at least one major resistance mutation. Resistance to fusion inhibitors was disregarded, as was resistance to some etravirine (Intelence) mutations that may take multiple forms.

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This shift in the composition of the study population appeared to influence long-term resistance trends. In 1999, between 50% and 57% of people were estimated to have at least one resistance mutation, while in 2007, the proportion had dropped to between 37% and 45%. Since resistance mutations generally persist, the change may seem paradoxical. But the researchers believe the most likely explanation to be the simultaneous growth of the low-risk subgroup and shrinking of the high-risk subgroup over time.

To distinguish between changes in the study population and changes in resistance levels, the researchers performed the same set of analyses on a cohort of individuals seen every year from 2002 through 2007. In other words, this “closed” cohort had no deaths or losses to follow-up, and all cases of resistance were carried forward. Resistance levels were estimated at 45% to 52% in 2002, and 49% to 55% in 2007. Importantly, increases in prevalence became smaller over the years.

Resistance change rates, calculated using lower-bound estimates for the open and closed cohort, were stratified according to the potency of cohort members’ first antiretroviral regimens. In the open cohort, resistance increased by 1.5% per year among people who had initiated therapy with a highly effective regimen that included an unboosted protease inhibitor (PI), and by 0.6% per year among those who had started on newer regimens (combinations including either a non-nucleoside reverse transcriptase inhibitor or a ritonavir-boosted PI). In the closed cohort, resistance increased by 1.2% per year for people who had started on unboosted PIs and by 1.6% per year for people who had started on newer regimens.

The researchers report that other studies based on analyses of antiretroviral resistance databases have found resistance rates of 76% to 90%. “However, patients who had undergone drug resistance tests are not representative of the entire [antiretroviral]-exposed population,” they note. “Studies of such patients tend to be biased toward patients who had experienced problems while undergoing therapy.”

The Swiss HIV Cohort Study appears to be very representative of diagnosed HIV-positive people in Switzerland, and the researchers suggest that findings in this study population may also apply to HIV-positive people in other countries with highly developed health care systems.

The researchers speculate that the prevalence of antiretroviral resistance will continue to decrease at the population level in developed countries “because of the observed dilution effects, but also, and more importantly, because durable therapy success can more often be achieved with newer drugs and thus the emergence of new drug resistance is considerably slowed.”

High rate of anal HPV infection, low rate of clearance and significant new infections in HIV-positive gay men

Anal infection with human papilloma virus was almost universal amongst HIV-positive gay men in a Canadian study published in the April 1st edition of the Journal of Infectious Diseases. The study also found that there was a high prevalence of infection with cancer-associated strains of human papilloma virus and that few mean cleared such infections in the course of the study.

Furthermore, during the three years of the study a significant proportion of men became infected with strains of human papilloma virus associated with a high risk of pre-cancerous and cancerous cell changes in the anus.

Circumcision trial shows how HIV and herpes amplify each other: circumcision protects against both

New findings from the South African randomised controlled trial (RCT) of circumcision have found that HIV and herpes simplex virus 2 (HSV-2) independently reinforce each others’ effects. People with one infection in the study were more likely to acquire the other infection. The study also found that circumcision protected men in the study against HSV-2 as well as HIV.

Response to Lipid-Lowering Therapy in Individuals with and without HIV Infection

It is widely recognized that antiretroviral therapy may adversely affect blood lipid levels in people with HIV-a potential risk factor for cardiovascular disease. This is particularly true of protease inhibitor-based regimens. However, it is not known whether dyslipidemia is more difficult to treat in HIV positive patients compared to HIV negative individuals.

In the current retrospective cohort study, published in the March 2009 issue of Annals of Internal Medicine, researchers from Kaiser Permanente Northern California and the University of California at San Francisco compared the effectiveness and safety of lipid-lowering therapy in patients with and without HIV infection.

The population evaluated was comprised of 829 patients with HIV infection and 6941 patients without HIV who were starting lipid-lowering therapy for elevated low-density lipoprotein (LDL) cholesterol or triglyceride levels. The investigators determined percentage change in lipids over 12 months and liver- and muscle-related clinical and laboratory adverse events.

The study authors noted several possible limitations of their study: "Laboratory measurements were not uniformly performed according to HIV status, and adequate fasting before lipoprotein testing could not be verified. In addition, results may not be completely generalizable to uninsured persons, women, or certain racial or ethnic minorities."

Based on their findings, the authors concluded that dyslipidemia, in particular hypertriglyceridemia (elevated triglycerides), is more difficult to treat in patients with HIV than in HIV negative individuals. However, they stated, "Patients with HIV infection receiving NNRTI-based antiretroviral therapy and gemfibrozil had triglyceride responses similar to those in patients without HIV infection."

Many cases of tuberculosis (TB) are preventable in HIV patients, according to a study published in the March 2009 issue of the International Journal of Tuberculosis and Lung Disease.

In this analysis, researchers from Vanderbilt University and the Comprehensive Care Center in Nashville, Tennessee determined the proportion of TB cases that could have been prevented among HIV positive individuals receiving medical care in the HAART era.

The investigators conducted an observational cohort study that included 360 HIV-infected patients with at least 2 outpatient visits at the Comprehensive Care Center between January 1, 1998 and December 31, 2005.

A potentially preventable TB case was defined as one in which the patient received no screening tuberculin skin test (TST) prior to TB diagnosis, or a case in which a patient with a positive screening TST did not complete treatment for latent infection.

Results

* Of 3601 HIV positive individuals in care, 29 developed TB. * Of these 29, 20 (69%) had not had a TST performed as part of routine screening. * Of the 9 patients who were screened, 4 had a positive test. * 3 of these individuals completed treatment for latent TB infection. * Of 29 total TB cases, therefore, 21 (72%) were potentially preventable with appropriate care.

Based on these results, the study authors concluded, "Most TB cases in this cohort were potentially preventable had the patients undergone a screening TST followed by treatment of latent infection if they had a positive TST."

Several nucleoside/nucleotide analog agents are active against hepatitis B virus (HBV), but development of drug resistance can present a barrier to long-term treatment success.

The EARLY Study (aka ETV-079) was an international (Canada, the U.S., and several countries in Asia) randomized, open-label trial comparing the newer nucleoside analog entecavir (Baraclude) versus the nucleotide analog adefovir (Hepsera).

Previously presented at the April 2007 annual meeting of the European Association for the Study of the Liver (EASL) and at May 2007 Digestive Disease Week (DDW) conference, the study findings have now been published in the January 2009 issue of Hepatology.

Nancy Leung

Nancy Leung and colleagues analyzed early antiviral activity and viral kinetic profiles of entecavir and adefovir in 69 hepatitis B "e" antigen (HBeAg) positive chronic hepatitis B patients who had not previously received nucleoside/nucleotide analogs. Participants were randomly assigned to receive either 0.5 mg/day entecavir or 10 mg/day adefovir for a minimum of 52 weeks.

* Entecavir demonstrated superior early antiviral activity and viral kinetic profiles compared with adefovir. * At week 12, the mean change from baseline in HBV DNA was -6.23 log10 copies/mL in the entecavir arm versus -4.42 log10 copies/mL in the adefovir arm (a mean difference of -1.58 log10 copies/mL; P < 0.0001). * Both drugs demonstrated biphasic viral kinetics, with a first phase of rapid HBV DNA decline lasting 10 days. * The advantage of entecavir over adefovir was apparent as early as day 10 (difference of -0.66 log10 copies/mL) * There was considerably less variability in the extent of HBV DNA reduction in the entecavir arm. * Both the mean decrease in HBV DNA and the proportion of patients achieving HBV DNA < 300 copies/mL were greater in the entecavir arm compared with the adefovir arm at weeks 2, 4, 8, 12, 24, and 48. * Early virological response was a significant predictor of subsequent virological response. * Patients with lower HBV DNA levels at day 10 were more likely to achieve HBV DNA < 300 copies/mL at week 48. * At week 48, just 1 patient (3%) in the entecavir arm had HBV DNA > 100,000 copis/mL, compared with 15 patients (47%) in the adefovir arm. * Both entecavir and adefovir were generally well tolerated.

Based on these findings, the study authors concluded, "Entecavir therapy resulted in earlier and superior reduction in HBV DNA compared with adefovir in nucleoside-naive HBeAg positive patients with chronic hepatitis B."

springerlink

Effect of Suppressing HIV Viremia on the HIV Progression of Patients Undergoing a Genotype Resistance Test after Treatment Failure

BackgroundTreatment guidelines for multi-experienced HIV patients have recently evolved from aiming to preserve immunity to achieving virological success, largely due to the availability of new antiretroviral drugs and drug classes. To assess the role of viral suppression on clinical progression following a genotypic resistance test (GRT), we have examined a database on patients failing to respond to combined antiretroviral therapy (cART).

MethodsPatients undergoing a GRT after failure to respond to cART between January 1999 and May 2006 were followed up to December 2006. Time-to-death or a new AIDS event/death were considered to be analysis end-points. Viral suppression (< 50 copies/ml [c/ml]) after GRT, a time-dependent covariate, was tested as predictor of disease progression.

ResultsOverall, 1,389 patients were included in this observational study. After the GRT, patients were followed up to 72 months (median 28 months, IQ range 13–51 months). During the follow-up, 124 patients (9%) died, and 86 (6%) experienced a new AIDS event. 774 patients (56%) achieved < 50 c/ml HIV-RNA. The results of an adjusted Cox model showed that undetectable HIV-RNA after the GRT was significantly associated with a lower risk of death (harzard ration HR 0.46, 95% confidence interval [CI] 0.27–0.76) and AIDS/death (HR 0.43, 95% CI 0.28–0.65). The adjusted hazard ratios suggested a twofold risk reduction. A threefold risk reduction of death related to achieved undetectable viral load was found in patients with resistance to more than one drug class and with CDC-C diagnosis; a fourfold reduction was found in patients with < 200 CD4+/mm3.

ConclusionsMaximal viral suppression has a large impact on HIV progression, particularly in heavily pre-treated individuals. Our findings support the latest treatment guidelines, which have rapidly evolved from an initial lack of indication to suggestions, and finally to strong recommendations for achieving the goal of suppressing viremia.

Combination antiretroviral therapy (ART) has markedly improved survival in HIV-infected patients, but not without significant adverse effects including ART-associated dyslipdemia and insulin resistance, which may in part contribute to an increased risk of cardiovascular events.

Other contributing factors to cardiovascular risk may include uncontrolled HIV replication, the effects of HIV and ART on vascular endothelium and inflammatory cytokines.

Diastolic dysfunction may be an early sign of cardiovascular disease. Our objective was to determine the prevalence of diastolic dysfunction in HIV-infected patients without cardiovascular symptoms.

We enrolled 91 subjects in a cross-sectional study of HIV-infected patients without cardiovascular symptoms between September 2004 and August 2005, to assess whether demographics, HIV-related factors, cardiac risk factors, and ART were associated with diastolic dysfunction. All subjects underwent two-dimensional transthoracic echocardiography with tissue Doppler imaging. Subjects were predominately male with a median age of 38 (interquartile range [IQR]: 33, 42) years and median ART duration 6.15 (IQR: 2.1, 8.4) years. Subjects had low Framingham risk scores.

This was not observed with prolonged use of either non-nucleoside or nucleoside reverse transcriptase inhibitors. A high prevalence of diastolic dysfunction (37%) in a cohort of HIV-infected patients on ART at low risk for AIDS and cardiovascular disease was demonstrated.

Results: HIV-1 DNA load was significantly higher in aged memory (CD45RO+ CD57+) when compared with memory (CD45RO+ CD57-) and naive (CD27+ CD45RO-) CD4+ T cells after HAART. Sequencing revealed no major drug resistance mutations in protease in all patients and appearance of resistance mutations in RT in just 1 patient. In 1 of 5 patients with undetectable viremia during treatment, RT M184 substitutions were detected. Phylogenetic analysis showed short genetic distances between patient sequences.

Conclusions: During long-term HAART, HIV-1 is able to persist in terminally differentiated CD4+ T cells as proviral DNA. Viral evolution was restricted, and in 80% of the patients with undetectable viremia, no sign of viral replication could be detected.

The preliminary data of this study suggest that more patients are likely to respond to the conventional HBV vaccine dose series if their CD4 counts are above 350 or they have undetectable viral load at the time of vaccination. In patients not responding to the conventional dose series, re-vaccinating with the high dose series may be a promising option. Future studies may include the comparison of high dose with conventional dose re-vaccination in HIV+ patients not responding to conventional dose vaccination series.

Progression of Liver Fibrosis in a Large Cohort of HIV Patients Over 4 Years: Emerging Contribution of Antiretrovirals and Metabolic Abnormalities

CONCLUSION

Progression of liver fibrosis in HIV patients is associated with classical factors, as HCV co-infection or alcohol abuse, and may be less frequent in patients treated with NNRTI-based regimens. In addition, elements of the metabolic syndrome (high body mass index, hyperglycemia) may equally contribute to LFP in HIV patients.

Researchers are looking into the antibodies that provide natural immunity

In a desperate attempt to reverse 25 years of failure to develop an Aids vaccine, scientists have a new approach: studying people who have been infected with HIV for many years without any signs of ill-health. The patients' secret? Natural immunity.

The researchers have investigated the virus-fighting antibodies found in the blood of six long-term survivors of HIV whose own immune systems appear to be capable of shrugging off the virus. Results of tests show that a prototype vaccine made from several of the antibodies produced by those long-term survivors can prevent HIV from infecting human cells. The experiments have been successful on human cells growing in a test tube. Now further trials are planned on laboratory animals and human volunteers.

The search for an Aids vaccine has suffered a series of setbacks over the years. The most recent was the failure of the most promising potential vaccine, in a major clinical trial by the US drug company Merck. The trial, which had involved thousands of volunteers, had to be abandoned at the end of 2007 because of fears that the trial vaccine might in fact make patients more susceptible to Aids.

Chinese scientists need to enroll more volunteers for a human test of the AIDS vaccine.Chinese scientists said on Saturday that they need to enroll more volunteers for a human test of the AIDS vaccine, as the research has moved into the second phase.

New Institute for Tuberculosis and HIV Research Created in South Africa

A groundbreaking partnership between the Howard Hughes Medical Institute (HHMI) and the University of KwaZulu-Natal (UKZN) in South Africa will establish an international research center focused on making major scientific contributions to the worldwide effort to control the devastating co-epidemic of tuberculosis and HIV and on training a new generation of scientists in Africa.

The Treatment Action Campaign (TAC) says the Free State moratorium on the provision of anti-retroviral (ARV) drugs for new patients was never lifted. The provincial government imposed the moratorium on the lifesaving drugs in November of 2008.

The U.S. tuberculosis rate hit an all-time low in 2008, but the infection continues to disproportionately affect minorities and immigrants, the U.S. Centers for Disease Control and Prevention reported on Thursday.

The CD4 binding loop flanks are variable and may contribute to a general mechanism for protecting proximal CD4 contact residues from neutralizing antibodies. The results have relevance for env-based vaccines that will need to expose critical CD4 contact residues to the immune system.

The data suggest a dual mechanism for durable control of HIV replication, consisting of viral fitness loss resulting from CTL escape mutations together with strong CD8 T-cell immune responses to the arising variant epitopes.

British scientists are all set to become the first in the world to use embryonic stem cells for producing unlimited amounts of synthetic human blood, paving the way for infection-free emergency transfusions.

Modern drug cocktails for these diseases are highly effective, reducing the viral load in the bloodstream to nearly zero. But at some point, the virus mutates, enabling it to evade the drugs and repopulate. As the viral tide rises, there are no outward symptoms in the patient, so the mutated strain is often discovered long after the virus has spread again.

The viral load detector, which relies on Benner's 12 letter system to tag DNA, may change that.

Researchers from the University of Pittsburgh and the Albert Einstein College of Medicine have developed an onsite method to quickly diagnose tuberculosis (TB) and expose the deadly drug-resistant strains of Mycobacterium tuberculosis that can mingle undetected with treatable strains.

Genomic Fossils In Lemurs Shed Light On Origin And Evolution Of HIV And Other Primate Lentiviruses

A retrovirus related to HIV became stably integrated into the genome of several lemurs around 4.2 million years ago, according to research led by Dr. Cédric Feschotte at the University of Texas, Arlington. The new analysis of prosimian immunodeficiency virus (pSIV) offers new insights into the evolution of lentiviruses.

Bone marrow stem cells may have cured one man of HIV (Hutter, et al. N Engl J Med. 2009;360:692-8). The patient had been infected with HIV for a while before developing acute myeloid leukemia. He received a stem-cell transplant from a donor who was homozygote for ?32 CCR5. Interestingly, the patient has remained without viral rebound 20 months after transplantation and discontinuation of antiretroviral therapy. Moreover, a search for HIV sequences in proviral DNA has also failed to prove that the virus could still be hidden in some reservoirs. In addition, the CD4+ T-cell count has returned to a normal range.

USA300-the major epidemic strain of methicillin-resistant Staphylococcus aureus (MRSA) causing severe infections in the United States during the past decade-inherits its destructiveness directly from a forefather strain of the bacterium called USA500 rather than randomly acquiring harmful genes from other MRSA strains.

Continuing the tradition of the recent landmark meetings held in Paris, Sydney, Atlanta, Rome, and Tokyo, the 13th ISVHLD will commemorate progress made in the global fight against viral hepatitis and liver disease and focus the field's attention on the key future challenges.

Massachusetts General Hospital (MGH) researchers are investigating a new way to block reproduction of the hepatitis C virus (HCV) – targeting not the virus itself but the human genes the virus exploits in its life cycle. In the March 19 Cell Host & Microbe, they report finding nearly 100 genes that support the replication of HCV and show that blocking several of them can suppress viral replication in cultured cells.

Isoniazid preventive therapy (IPT) combined with antiretroviral therapy (ART) reduced the risk of developing active tuberculosis (TB) in people with HIV by almost 90% compared with no treatment, a South African study has shown.

On March 20, 2009, the Food and Drug Administration (FDA) approved a generic formulation of stavudine for oral solution, 1 mg/mL. Stavudine is a Nucleoside Reverse Transcriptase Inhibitor (NRTI) indicated for used in combination with other antiretroviral agents in the treatment of HIV infection.

South Africa is trying a new approach to controlling drug-resistant tuberculosis - treating people at home rather than in isolation hospitals surrounded by barbed wire and baton-wielding guards, health officials said Monday .

The colourful new magazine of the International Community of Women Living with HIV/AIDS (ICW) in Latin America and the Caribbean has a modern look and provides not only information but articles on fashion and entertainment. It is also the perfect size to carry in a purse.

Coenzyme F420, a small molecule that helps certain enzymes transfer electrons, is found in microorganisms known as methane-producing archaea, some of which thrive in extreme environments. It also helps the bacterium that causes tuberculosis (TB) to survive the defenses of the human immune system. Scientists have now discovered at least one way F420 helps to arm the pathogen. The research will appear in the early online issue of the Proceedings of the National Academy of Science (PNAS) during the week of March 23, 2009, in the article, "Conversion of NO2 to NO by Reduced Coenzyme F420 Protects Mycobacteria from Nitrosative Damage," by Endang Purwantini and Biswarup Mukhopadhyay, both with the Virginia Bioinformatics Institute (VBI) at Virginia Tech.

Tenofovir (Viread) during Pregnancy: Findings from the Antiretroviral Pregnancy Registry

"As of March 20, 2009, no overall increase in prevalence or any specific pattern of congenital anomalies has been detected with the use of tenofovir in 800 live births through prospective voluntary reporting to the APR," the study investigators concluded.

Is Tenofovir an Option for Prevention of Mother-to-child HIV transmission?

The use of antiretroviral therapy by HIV positive mothers during pregnancy and labor and babies for a brief period after birth can reduce the risk of mother-to-child HIV transmission to less than 2%. Zidovudine (AZT; Retrovir) was the drug first studied for this purpose, and single-dose nevirapine (Viramune) is widely used in resource-poor countries.

Saskatchewan has seen a dramatic increase in HIV infections, putting the province far above the national average, health officials say.

There was a 40 per cent increase in new cases of HIV — the virus that causes AIDS — detected last year, compared to 2007. That made for 174 new cases in 2008, the province’s chief medical health officer said Monday.

For the third year running MTV Networks International and The Body Shop have announced they are working together to raise funds for MTV’s Staying Alive Foundation with the launch of their “Yes, Yes, Yes – To Safe Sex” campaign.

Two Miami-Dade doctors and their medical assistants have pleaded guilty to plotting to defraud Medicare of $10 million with phony claims for HIV-infusion treatments that patients did not need or receive, federal prosecutors said Monday.

More than 50 percent of Tuberculosis (TB) patients in Swaziland are reportedly also infected with HIV, and it is estimated that this figure is well below the actual percentage of co-infected patients. This video [see website] highlights a forgotten humanitarian emergency, showing the link between HIV and TB, and the importance of early diagnosis.

LONDON--(BUSINESS WIRE)--The drive to discover and develop new oral treatments for tuberculosis (TB), which could save millions of lives in developing countries, will receive an £18 million boost, International Development Minister Ivan Lewis announced today.

"Nearly 30 years into the AIDS epidemic, we are able to access our progress in tackling the disease with both increased knowledge and the benefit of hindsight," former UNAIDS Executive Director Peter Piot of Imperial College London, who also serves as an adviser on global health strategy to the Bill & Melinda Gates Foundation;

Eating more low-fat dairy products alongside fruit and vegetables boosts nutrient intakes and may help HIV patients to maintain a healthy body weight, according to research published in the American Journal of Clinical Nutrition.

A new report from the World Health Organization shows that while the total number of new TB cases worldwide remained stable in 2007, and the proportion of people becoming ill with TB continued to fall, the proportion of TB deaths that are HIV related is now thought to be 25 per cent, which is twice as many as previously estimated.

There were in excess of 500,000 cases of multidrug-resistant tuberculosis (MDR-TB) in 2007, according to figures released in the World Health Organization 2009 Global Tuberculosis Control report. But, says WHO, less than 30,000 cases of MDR-TB were notified in 2007, and just 1% of the global population of MDR-TB cases received appropriate treatment.

Argos Therapeutics Presents Research on the Development and Evaluation of Immunotherapies for HIV - Abstracts Presented at Keystone Symposia on HIV Immunobiology

DURHAM, N.C. - Argos Therapeutics today announced the presentation of an abstract related to its Arcelis(TM) HIV immunotherapy program at the Keystone Symposia Global Health Series conference on HIV Immunobiology, held March 22 - 27 in Keystone, CO. The poster presentation details important research on the immunosuppressive properties of HIV, and how this research may influence the development of HIV immunotherapies.

WOBURN, Mass. - Aphios Corporation today announced entering into a Collaborative Research and Development Agreement with VivaCell Biotechnology Espana S.L., Cordoba, Spain to develop a combination therapy for the treatment of HIV latency.

Cailhol J et al. - The current World Health Organization recommendation to initiate combination antiretroviral therapy for immunocompromised women as early as possible during pregnancy for their own health and for the prevention of HIV mother-to-child transmission is likely to also decrease the incidence of IUGR. Encouraging immunocompromised HIV-infected women who plan to become pregnant to wait until immune restoration has been achieved may help to reduce the risk of IUGR.

Epidemiologic Characteristics and Natural History of HIV-1 Natural Viral Suppressors

Sajadi MM et al. - The NVS cohort has demonstrated remarkable stability and a low rate of progression over many years. Detailed evaluations of viral-host immune regulatory factors associated with persistent HIV-1 natural viral suppression, and loss of such suppression, has the potential to provide important new insight in HIV pathogenesis and future immune regulatory targeted preventive and therapeutic research.

PRINCE GEORGE'S PUBLIC HEALTH - County Still No. 2 in Md. For STDs, Official Says

Prince George's County continues to have the second-highest rate of sexually transmitted diseases in Maryland and the second-highest number of reported AIDS and HIV cases, according to the county's top health official. Prince George's trails only Baltimore in both categories.

JOHANNESBURG/LONDON, March 25 (Reuters) - GlaxoSmithKline Plc (GSK.L) plans to take a significant stake in Aspen Pharmacare Holdings Ltd (APNJ.J) to strengthen its partnership with the South African drugmaker, people familiar with the situation said.

Researchers at the Tulane University School of Medicine, New Orleans, Louisiana have discovered that the HIV-1 protease inhibitors (PIs), such as nelfinavir included in highly active antiretroviral therapy (HAART) regimen for the treatment of HIV-1 patients, induce deleterious effects on insulin secretion mediated through the oxidative stress pathway.

Wasting, anaemia predict very high short-term risk of death in Asian ARV patients

Severe anaemia or a body mass index below 18 were good predictors of a very high risk of developing AIDS or dying within the following three months among Asian patients receiving antiretroviral therapy, and could be used in the absence of CD4 cell counts to identify patients in need of close attention after starting treatment, researchers from South-East Asia and China report in the journal Clinical Infectious Diseases.

Therapists still offering treatments for homosexuality despite lack of evidence

A significant minority of psychiatrists and therapists are still attempting to help lesbian, gay and bisexual clients become heterosexual despite lack of evidence that such treatment is beneficial or even safe, according to research funded by the Wellcome Trust.

LUSAKA, MAR 23 (IPS) - Parliamentarians across the Southern African Development Community (SADC) have failed to put HIV on the political agenda.

"Considering SADC is at the epicentre of the HIV pandemic, not enough is being done to address it. HIV has a very negative impact on [the region's] development," lamented SADC Parliamentary Forum secretary general Dr. Kasuko Mutukwa at a media briefing in Zambia's capital Lusaka on Mar. 18.

Your favorite fast food restaurant is often like your favorite city: Visit some neighborhoods and you live the high life. Visit others and you’re just plain asking for trouble. And that’s where Eat This, Not That! comes in: We’ve analyzed and graded 66 different chain restaurants—fast food and sit-down—to determine which ones have healthy options, and which could turn out to be diet disasters.

What we found will surprise you. Specifically, some of the fast food joints you’ve come to think of as terrible for you actually ranked alright—McDonald’s scored a B+, for example, so the Micky D’s drive-thru just might be your fast-lane to weight loss. Something even more shocking, though: more than half of the sit-down restaurants we graded ended up with our lowest scores!

To separate the commendable from the deplorable, we calculated the total number of calories per entrée. This gave us a snapshot of how each restaurant compared in average serving size—a key indicator of unhealthy portion distortion. Then we rewarded establishments with fruit and vegetable side-dish choices, as well as offering whole-wheat bread. Finally, we penalized places for excessive amounts of trans fats and menus that tempt you with fat-laden desserts. Hey, if the neighborhood is crowded with shady characters, sooner or later, one of them will jump you.

Here’s our restaurant report card for some of the unhealthiest restaurants in America. It’ll help you stay on the safer side of town.

D+Baskin-RobbinsWe thought we'd see some improvements after we identified Baskin's Heath Shake as the Worst Drink on the Planet. All they did was lower it from 2,300 to 1,900 calories, leaving an almost equally egregious drinkable disaster to set back unsuspecting sippers. It’s typical of the menu there; B-R’s soft serve is among the most caloric in the country, the smoothies contain more sugar than fruit, and most of what Baskin sticks into a cup winds up with more fat than what'll end up on your plate at a steakhouse buffet. Check out our complete list of the 20 Unhealthiest Drinks in America to see the other liquid offenders. If you learn how to make smart choices when you sip, you can lose a few pounds a month—without giving up your favorite foods, or ever dieting again.

SURVIVAL STRATEGY: With frozen yogurt, sherbet, and no-sugar-added ice cream, Baskin's lighter menu is the one bright spot. Just be sure to ask for your ice cream in a sugar or cake cone—the waffle cone will swaddle your treat in an extra 160 calories.

D+Carl’s Jr.Most fast-food restaurants today are making at least some attempt to offset their bulging burgers and deep-fried sides with healthier options such as lean sandwiches or yogurt parfaits. But Carl's Jr. is swimming against the nutritional tide, trying to attract those with hearty appetites and less concern about fat, salt and calories. The lightest item on the breakfast menu, for instance, is the Hash Brown Nuggets—but even they have 21 grams of fat, and 5.5 of them are trans fats. (As a rule, you should try to get 2 grams or fewer of the stuff in an entire day!) The burgers are worse, and there's not a side on the menu that hasn't been given a long, bubbling bath in their trans-fatty frying oil.

SURVIVAL STRATEGY: Find another place to grab lunch. Failing that, you should settle on either the Charbroiled Chicken Salad with Low-Fat Balsamic Dressing or the Charbroiled BBQ Chicken Sandwich—the only sandwich on the menu with fewer than 400 calories.

D+Denny’sToo bad the adult menu at Denny's doesn't adhere to the same standard as the kids' menu. The famous Slam breakfasts all top 800 calories, and the burgers are even worse. The Double Cheeseburger is one of the worst in the country, with 116 grams of fat, 7 of which are trans fats! (This explains why it made our list of the worst burgers in America (and what you should eat instead). Make sure you try to avoid it (and all others on the list) whenever possible.

SURVIVAL STRATEGY: The Fit Fare menu gathers together all the best options on the menu. Outside of that, stick to the sirloin, grilled chicken, or soups. For breakfast, order a Veggie Cheese Omelet or create your own meal from a la carte options such as fruit, oatmeal, toast, and eggs.

D+Dairy QueenDairy Queen’s taste for excess rivals that of other fast-food failures such as Carl's Jr. and Hardees. But unlike Carl's, DQ offers an avalanche of ice cream creations to follow up its sodium-spiked, trans-fatty foods. Here's a look at one hypothetical meal: a Bacon Cheddar GrillBurger with Onion Rings and a Small Snickers Blizzard is a staggering 1,740-calorie meal with 2,640 mg sodium and 83 grams of fat—2 grams of which are trans fats.

SURVIVAL STRATEGY: Play solid defense. Skip elaborate burgers, fried sides, and specialty ice cream concoctions entirely. Order a Grilled Chicken Sandwich or an Original Burger, and if you must have a treat, stick to a small soft-serve or a small sundae.

D+Ruby TuesdayThe chain earned its fame from a hearty selection of hamburgers. The problem: They average 75 grams of fat a piece—more than enough to exceed the USDA's recommended limit for the day. Even the veggie and turkey burgers have more than 850 calories! The chain rounds out its menu with a selection of appetizers that hover around 1,000 calories (supposedly to be split 4-ways), a smattering of high-impact entrées like potpie and ribs, and a sloppy selection of salads that is just as bad.

SURVIVAL STRATEGY: Solace lies in the three Ss: steak, seafood, and sides. Sirloins, salmon, and shrimp all make for relatively innocuous eating, especially when paired with one of Ruby Tuesday's half dozen healthy sides such as mashed cauliflower and baby green beans. Other than that, impersonate Mick Jagger and think about occasionally saying goodbye to Ruby Tuesday!

DChili’sFrom burgers to baby back ribs, Chili's serves up some of the saltiest and fattiest fare on fast-food row. In fact, with 3,810 mg of sodium and 122 grams of fat, Chili's Smokehouse Bacon Triple Cheese Big Mouth Burger earns the distinction as being one of the worst burgers in America. The Guiltless Grill menu is Chili's attempt to offer healthier options, but with only eight items and an average sodium count of 1,320 mg, there’s meager hope for nutritional salvation.

SURVIVAL STRATEGY: There's not too much to choose from after you omit the ribs, burgers, fajitas, chicken, and salads. You're better off with a Classic Sirloin and steamed vegetables or broccoli. Another decent option is the Chicken Fajita Pita with Black Beans and Pico de Gallo. A lot of the appetizers, while delicious, are worrisome too—one from Chili’s made it on our list of Worst Appetizers in America.

DUno Chicago GrillUno has some serious strikes against it: The chain invented the deep-dish pizza, they encouraged gluttony with their Bigger and Better menu, and in 1997 they faced false-advertising charges for erroneously claiming that some of their pizzas were low in fat. They've cleaned up some of the more conspicuous health hazards and have increased nutritional transparency at all of their stores, but from appetizers to desserts, this menu is still riddled with belt-busting fat.

SURVIVAL STRATEGY: First off, cast aside the bloated breadstick that Uno tries to sneak onto most plates. Next, choose flatbread over deep-dish pizzas—it could save you more than 1,000 calories. Beyond that, stick to soups or entree items served with Mango Salsa.

DChevy’sDon't let the made-fresh-daily shtick distract you; Chevy's massive portions push many of the meals beyond the 1,000-calorie threshold. The taco trader’s menu has three strikes against it: 1.) the consistently high amount of fat in its entrees (the average salad has 67 grams); 2.) the outrageous salt levels that make it difficult to find a meal with fewer than 2,000 mg of sodium (you should get around that amount in an entire day of eating); and 3.) the chain earns its poor score by failing to offer complete nutritional disclosure. It provides no information for its appetizers or quesadillas, for instance, and although it maintains it uses trans-fat free oils, there's no trans-fat data for the full entrees.

SURVIVAL STRATEGY: The best items on the menu are the Homemade Tortilla Soup, with just 393 calories and a full 26 grams of protein, and the Santa Fe Chopped Salad, which has only 470 calories when you order it without cheese. If you can't resist an entrée, order it without all the fixin's—tamalito, rice, sour cream, and cheese. That should knock more than 300 calories off your meal.

D-On the BorderOn the Border is a subsidiary of Brinker International, the same parent company that owns Chili's and Romano's Macaroni Grill. It should come as no surprise then that this chain is just as threatening to your health as its corporate cohorts. The overloaded menu offers appetizers with 120 grams of fat, salads with a full day's worth of sodium, and taco entrées with an horrific 960 calories—and that’s the calculation without rice and beans. Border crossing is a decidedly dangerous enterprise.

SURVIVAL STRATEGY: The Border Smart Menu highlights four items with fewer than 600 calories and 25 grams of fat. Those aren't great numbers considering they average 1,800 mg of sodium apiece, but that's all you've got to work with.

D-Romano’s Macaroni GrillFor years now we've been on Romano's case to clean up the menu at the beloved Macaroni Grill. So far we've had no luck. This Italian grease spot serves some of the worst appetizers in the country, offers not one dinner entrée with fewer than 800 calories, and hosts no fewer than 60 menu items with more than 2,000 mg of sodium—almost an entire day’s worth of the salt! A select few menu items earn the restaurant's Sensible Fare logo—a fork with a halo over it—but unfortunately these items can still carry up to 640 calories and 25 grams of fat.

SURVIVAL STRATEGY: Macaroni Grill will let you build your own dish. Ask for the marinara over a bed of the restaurant's whole-wheat penne, and then top it with grilled chicken and steamed vegetables. Just beware their salads—one of them made our list of America’s Worst Salads!

D-Baja FreshIt's a surprise Baja Fresh's menu has yet to collapse under the weight of its own fatty fare. About a third of the items on the menu have more than 1,000 calories, and most of them are spiked with enough sodium to melt a polar icecap. Order the Shrimp Burrito Dos Manos Enchilado-Style, for instance, and you're looking at 5,130 mg sodium—that's more than 2 days' worth in one sitting!

SURVIVAL STRATEGY: Unless you're comfortable stuffing 110 grams of fat into your arteries, avoid the nachos at all costs. In fact, avoid almost everything on this menu. The only safe options are the tacos, or a salad topped with salsa verde and served without the belly-busting tortilla bowl.

FApplebee’s, IHOP, Outback, T.G.I. Friday’sThese titans of the restaurant industry are among the last national chains that don’t offer nutritional information on their dishes. Even after years of badgering their representatives, we still hear the same old excuses: it’s too pricey, it’s too time-consuming, it’s impossible to do accurately because their food is so fresh, or we have too much variety. Our response is simple: If nearly every other chain restaurant in the country can do it, then why can’t they?

Your Survival Strategy: Write letters, make phone calls, beg, scream, and plead for these restaurants to provide nutritional information on all of their products. Here’s the contact information for each of the restaurants that refuse to fess up!

For a comprehensive Restaurant Report Card on all of the other fast food and chain restaurants, please click here for the whole list.

You can also join the Eat This, Not That! premium Web site, which acts as a 24-hour-a-day online personal nutritionist, offering other useful tips, tricks, hints, and insights into navigating the restaurant industry’s nutritional landmines and making the best eating choices each and every time. Or, check out the regular site for other great articles—like the 20 worst foods of 2009 and the 20 most sugar-packed foods in America.

Avexa Reaches First Critical Evaluation Point for new NRTI ATC's Phase III Trial

Avexa Limited (ASX:AVX) today announced that the last patient enrolled in the initial two dose phase of the apricitabine (ATC: 0.24, 0, 0%) Phase III trial has passed the week 16 time point. This significant event triggers the start of the data analysis for the Week 16 results. The company is expecting to announce the results in the second quarter of 2009.

A resistance score incorporating all mutations ever detected in a person's virus--not just mutations in the last genotype--afforded a deeper look at potentially inactive antiretrovirals in a two-center study [1]. The results confirm and extended earlier findings in a Canadian cohort [2]. Federico Garcia and colleagues in Granada and London studied 227 people who had two or more genotypic resistance tests while taking antiretrovirals. They figured two genotypic susceptibility scores (GSS)--one based only on the latest genotype and one based on every genotype for each patient. Using the Stanford, ANRS, and Rega genotypic resistance interpretive systems, the investigators scored individual antiretrovirals as 1 (susceptible), 0.5 (intermediate resistance), or 0 (high-level resistance).

EHDRW: Resistance Testing Is Not Standard-of-Care After Antiretroviral Failure in Europe

Despite long-standing guidelines recommending resistance testing after virologic failure, more than two thirds of EuroSIDA cohort members had no recorded resistance test after taking a failing regimen 4 months or longer [1]. In people who did get a resistance test after failure, time from failure to testing averaged about 7 months

..

Kaplan-Meier analysis calculated the following probabilities of having a resistance test after failure:

Improved antiretroviral regimens and better care greatly lowered the proportion of people with a high or detectable viral load in a large Milan cohort at the L. Sacco Hospital [1]. But that viral load decline from before 2000 to 2006-2007 did not result in a significant drop in proportions of untreated people infected with resistant virus. Transmission of drug-resistant HIV persisted especially among gay men.

..

The Milan team also charted viral loads in 369 newly diagnosed people, including 103 (28%) recently infected people (seroconverters) with a known date of seroconversion. This subgroup was mostly male (84%), 52% were infected during gay sex, and 44% were infected during sex between men and women. During the five study periods, proportions of people in the overall group with a viral load below 1000 or 50 copies rose significantly (P < 0.0001 for both measures):

EHDRW: Genotyping for Coreceptor Use Concordant With Trofile in PBMCs and Plasma

Three genotyping systems to predict viral coreceptor use proved 70% or more concordant with the Trofile phenotyping assay in plasma and peripheral blood mononuclear cells (PBMCs), according to results of a 73-person French study [1]. Prevalence of maraviroc-related resistance mutations was equivalent in plasma and PBMCs.

The study showed that "intensively lowering blood glucose to a target of 81 to 108 mg/dL does not benefit critically ill patients and may well increase their risk of dying," lead author Dr Simon Finfer (the George Institute for International Health, Sydney, Australia) told heartwire. "There is no benefit to be gained beyond a target of less than 180 mg/dL."

A research team at the Scripps Research Institute has obtained the first glimpse of a protein that keeps certain substances, including many drugs, out of cells. The protein, called P-glycoprotein or P-gp for short, is one of the main reasons cancer cells are resistant to chemotherapy drugs. Understanding its structure may help scientists design more effective drugs.

DNA from human papilloma virus type 16 (HPV16) and HPV type 18 (HPV18) were found in the majority of invasive cervical cancers in New Mexico in the 1980s and 1990s, according to a population-based study published in the March 24 online issue of the Journal of the National Cancer Institute.

A coalition of AIDS activists known as the Coalicion de Activistas por el Acceso Universal, spearheaded by AIDS Healthcare Foundation (AHF), which operates four free treatment clinics in Mexico (Puerto Vallarta, Cancun, Tuxtla Gutierrez and Pachuca), declared victory today in its campaign to lower drug prices and improve access to lifesaving AIDS treatments in Mexico. As a result of the coalition's prolonged, multinational campaign to raise awareness about the high price charged by Abbott Laboratories Inc. for its key AIDS drug, Kaletra in Mexico, the company has cut its price by twenty percent -- from $4688.00 pesos MXN per patient per month to $3750.40 MXN. The new lower price was published for the first time last Friday on the website of CENSIDA, Mexico's National Center for the Prevention and Control of HIV/AIDS.

Steady-State Pharmacokinetics of Abacavir in Plasma and Intracellular Carbovir Triphosphate following Administration of Abacavir at 600 Milligrams Once Daily and 300 Milligrams Twice Daily in Human Immunodeficiency Virus-Infected Subjects

This study showed that ABC 600 mg QD and ABC 300 mg BID regimens led to similar intracellular CBV-TP C values, thus providing pharmacokinetic support for the interchangeability of these two regimens. Women had higher intracellular CBV-TP exposure than did men.

Trends in Hospitalizations for AIDS-Associated Pneumocystis jirovecii Pneumonia in the United States (1986–2005)

While there have been significant reductions in hospitalizations and hospital mortality for AIDS-associated PCP over the last twenty years, these reductions have not been homogenous across demographic subpopulations and geographic regions and point to new at-risk populations. Furthermore, mortality in severe cases of PCP that require mechanical ventilation has improved substantially.

Radiology services for children in HIV- and TB-endemic regions: scope for greater collaboration between radiologists and clinicians caring for children

This review aims to heighten awareness of issues confronting radiologists and clinicians caring for children and to encourage greater collaboration between these two disciplines in HIV- and TB-endemic regions. The Child-Friendly Healthcare Initiative is discussed, emphasizing opportunities to promote child friendliness in radiology services.

Vertically transmitted HIV infection is a major problem in the developing world due to the poor availability of antiretroviral agents to pregnant women. HIV is a neurotrophic virus and causes devastating neurological insults to the immature brain. The effects of the virus are further compounded by the opportunistic infections and neoplasms that occur as a result of the associated immune suppression. This review focuses on the imaging features of HIV infection and its complications in the central nervous system. Vertically transmitted HIV infection is a major problem in the developing world due to the poor availability of antiretroviral agents to pregnant women. HIV is a neurotrophic virus and causes devastating neurological insults to the immature brain. The effects of the virus are further compounded by the opportunistic infections and neoplasms that occur as a result of the associated immune suppression. This review focuses on the imaging features of HIV infection and its complications in the central nervous system.

Community factors shaping HIV-related stigma among young people in three African countries

The results demonstrate a clear influence of the community environment on shaping HIV-related stigma among young people. The elements of the community that were significantly associated with HIV-related stigma were the economic and behavioral aspects of the community environment, and there was no evidence of relationships between demographic patterns and HIV-related stigma. Behavioral change interventions must address HIV-related stigma in order to encourage behavior change, and must take into account the social, economic and cultural environments in which young people exist.

Because both HIV-positive and HIV-negative men often seroguess, education and prevention programs should address the fact that HIV-negative men who engage in UAI due to this practice may be at high risk of HIV infection. HIV prevention should take into account these contemporary changes in behaviors, especially among HIV-negative gay men.

Slow to share: social capital and its role in public HIV disclosure among public sector ART patients in the Free State province of South Africa

This study identified bonding social capital as a leverage to maximize potential benefits and minimize potential risks in order to shift the balance toward consistent public disclosure. Furthermore, the importance of bridging social capital initiatives is demonstrated, especially for the most vulnerable patients, those who cannot capitalize their bonding social capital by disclosing their HIV serostatus to family and friends at the start of treatment.

The influence of the patients' educational levels on socioeconomic, clinical, immunological and virological endpoints

The patient's educational level influences clinical and immunological outcomes of HIV infection. This impact is probably mediated through differences in the long-term effects of treatment, as a result of adherence to antiretroviral therapy and to medical indications. The evaluation of social aspects such as the patient's education should be incorporated into routine clinical practice to improve the results of treatment.

HIV treatment does not cause cryptogenic liver disease. Nor is there an association between any individual anti-HIV drug and the development of the disease, UK investigators report in the April edition of the Journal of Acquired Immune Deficiency Syndromes. Their findings contradict the results of earlier research that suggested an association between ddI (didadosine, Videx) treatment and the development of cryptogenic liver disease.

Patients co-infected with HIV and hepatitis C virus whose HIV treatment is suppressing their viral load to undetectable levels have comparable CD4 cell count increases to those seen in patients who are only infected with HIV, investigators report in the April 15th edition of the Journal of Acquired Immune Deficiency Syndromes.

A score based on resistance mutations and type of antiretrovirals given in a salvage regimen predicted response to maraviroc in people enrolled in the MOTIVATE 1 and 2 trials of this CCR5 antagonist [1]. This result reflects findings of an earlier study in which a weighted phenotypic resistance score predicted response to maraviroc [2]. Nearly 80% of MOTIVATE participants randomized to maraviroc had a viral load under 50 copies at trial week 48 if they began treatment with more than 50 CD4s and had a weighted genotypic optimized background therapy susceptibility score (g-wOBTSS) indicating an active background regimen.

Washington, D.C.--Congressman Eliot Engel (D-NY), Speaker Nancy Pelosi (D-CA) and Congresswoman Ileana Ros-Lehtinen (R-FL) re-introduced the Early Treatment for HIV Act" (ETHA) on Thursday to allow states to extend Medicaid coverage to low-income individuals with the HIV virus before it advances to full-blown AIDS. Currently, most lower-income persons must first become disabled by AIDS before receiving Medicaid provided care and treatment, which could have prevented them from becoming seriously ill, and at which point treatment is far more expensive.

"In our cohort, temporary ART discontinuation early in pregnancy is more frequent in women receiving HAART, probably because of the fear of drug toxicity in the embryo. However, temporary discontinuation led to a 10-fold increase in the rate of MTCT, overcoming all other risk factors, except for the independent factor of high plasma viral RNA load at delivery.. When viral load increased by 1 log10 copies/mL, the risk of MTCT was, indeed, more than doubled."..."counseling on the temporary discontinuation of ART in the first trimester should consider both the need for maternal health [7] and the increased risk of HIV-1 transmission to the offspring"...."Overall, the rate of MTCT in the whole cohort was 1.3% (95% CI, 0.7%-2.3%). The rate of MTCT among children born to mothers who had ART interrupted in the first trimester was 4.9% (95% CI, 1.9%-13.2%), and the rate of MTCT among children born to mothers who had ART interrupted in the third trimester was 18.2% (95% CI, 4.5%-72.7%)."

Researchers at the Tulane University School of Medicine, New Orleans, Louisiana have discovered that the HIV-1 protease inhibitors (PIs), such as nelfinavir included in highly active antiretroviral therapy (HAART) regimen for the treatment of HIV-1 patients, induce deleterious effects on insulin secretion mediated through the oxidative stress pathway.

A team of researchers at Mount Sinai School of Medicine and the UC Davis Center for Biophotonics Science and Technology have for the first time captured on video the transfer of human immunodeficiency virus (HIV) from infected to uninfected T cells through structures called virological synapses. The breakthrough study, which could lead to new methods to block the transmission of HIV, will be published in the March 27 edition of Science.

A United Nations report says almost three million people in developing countries are now receiving drugs for H.I.V. This is an increase of almost one million people from two thousand six. Still, the hope was to reach three million by two thousand five.

Treatment for Hepatitis B: When to Start, What to Use, and When to Stop

At the 13th International Symposium on Viral Hepatitis and Liver Disease held in Washington March 20-24, 2009, invited experts presented their views on a variety of important issues related to the treatment and management of hepatitis B and C.

Chronic Hepatitis B Patients May Need to Begin Liver Cancer Screening at a Younger Age than Currently Recommended

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Epidemiologic studies have shown that 60% of all HCC cases are related to hepatitis B virus (HBV) infection.

Tuberculosis (TB) is the leading cause of death for people with HIV/AIDS worldwide, and a new report from the World Health Organization (WHO) indicates that people with HIV/AIDS account for 25% of all TB deaths.

DURBAN, South Africa, March 28 /PRNewswire/ -- Following seven years of continuing growth at its first free international AIDS treatment site outside of the United States, AIDS Healthcare Foundation (AHF), the largest AIDS group in the US, which currently provides medical care and services to more than 98,000 individuals in 21 countries worldwide in the US, Africa, Latin America/Caribbean and Asia, will launch a new, expanded state-of-the-art clinic location in Umlazi, Durban, South Africa.

Stress, needs, and quality of life of family members caring for adults living with HIV/AIDS in Taiwan

A family-centered care for PLWHA and their families in the community is crucial to improve quality of care and to prevent family's overload, particularly for families with no alternative manpower and for those being PLWHA's parents.

Interviews elucidated the difficulty that parents have in discussing their own HIV status and more general sexual health issues with their children. Parents and other guardians require support in managing age-appropriate disclosure to their children. This may further enable access to forums that can help children cope with their fears about the future and develop life skills in preparation for dealing with relationships of a sexual nature and sexual health as children move into adulthood. In developing such support mechanisms, changing family roles in Botswana need to be taken into consideration and the role of other family members in the upbringing of children in Tswana society need to be recognised and utilised.

Which factors hinder the decision of Polish HIV-positive patients to take up antiretroviral therapy

The therapy is generally not discussed with the patients for whom it is not currently indicated, which may contribute to the fixation of fears and prejudices. Doctors who treat HIV-positive patients should be aware of the prejudices and fears their patients have towards antiretroviral therapy in order to react properly and by means of the available antiretroviral drugs help prolong life and improve its quality.

Relational contexts in adjustment to pregnancy of HIV-positive women: relationships, social support and personal adjustment

Profile analysis suggests a greater importance of social support provided by the partner and both parents, especially the support provided by the mother. At the same time, it seems to highlight the buffering hypothesis of social support, which could be understood as a protection factor in the adjustment of HIV-infected women' to pregnancy.

The authors used an allele-specific real-time PCR assay to explore the presence of K103N and M184V minority species among primary human immunodeficiency virus (HIV) infections and their potential influence in HIV transmission. Thirty randomly chosen antiretroviral drug-naive patients lacking both the K103N and the M184V mutations as determined by conventional sequencing methods were studied, and K103N and M184V viral minority species were found in three and four patients, respectively.

Mass hepatitis B vaccination in children decreases the carriage of the virus, and the diseases associated with acute and chronic infection, including hepatocellular carcinoma. Challenges that need to be solved to expand mass vaccination, and the strategies towards elimination and eventual eradication of hepatitis B in the world are also discussed.

"In healthy men and women starting rosuvastatin therapy in the JUPITER trial, achievement of target concentrations of LDL cholesterol less than 1·8 mmol/L (<70 mg/dl) and hsCRP less than 2 mg/L was associated with improved event-free survival compared with achievement of neither target or with achievement of reduced LDL cholesterol alone.

We recorded a 79% reduction in hazard in participants who achieved the targets of LDL cholesterol less than 1·8 mmol/L and hsCRP less than 1 mg/L (table 4, figure 2). In similar analyses restricted to participants who achieved LDL cholesterol concentrations less than 1·8 mmol/L, those who achieved hsCRP concentrations less than 1 mg/L had better clinical outcomes than did those who did not."

Orlando, FL (updated March 29, 2009) - The use of rosuvastatin (Crestor, AstraZeneca) in healthy individuals reduced the risk of symptomatic venous thromboembolism (VTE), and the treatment effect was similar to and independent of the previously reported reduction in cardiovascular events [1].

The findings, from the Justification for the Use of Statins in Primary Prevention: An Intervention TrialEvaluating Rosuvastatin (JUPITER), presented during a late-breaking clinical-trials session at theAmerican College of Cardiology 2009 Scientific Sessions and published online today in the New England Journal of Medicine, suggest a widening use of statins in different patient populations.

Pretreatment low-frequency K103N mutations correlated with virologic failure of a nonnucleoside-based regimen in a British case-control study [1]. Four of 7 patients had transmitted nonnucleoside resistance mutations that could be detected only with a real-time PCR assay that identifies virus making up 0.3% to 1% of a viral population. Standard bulk sequencing sees virus only when it makes up about 20% or more of a viral population.

EHDRW: No Resistance to Darunavir or Lopinavir After 96 Weeks in ARTEMIS

No major protease mutations arose upon failure of darunavir/ritonavir or lopinavir/ritonavir in a 96-week analysis of the ARTEMIS trial, which enrolled previously untreated people [1]. In all darunavir and lopinavir failures analyzed to date, HIV remained susceptible to all protease inhibitors (PIs)--including the study PI--after failure. These results do not make it easier to explain why ARTEMIS researchers recorded significantly more failures with lopinavir than with darunavir at 96 weeks. Some evidence suggested worse adherence to lopinavir can be blamed.

EHDRW: Weighted Genotyping Scores Work Equally Well in Predicting Response to Etravirine

Two weighted genotypic scores for predicting response to the nonnucleoside etravirine yielded highly similar results in a 4000-sample analysis and in a review of more than 300 DUET trial participants [1]. Both scores--one devised by Tibotec (etravirine's maker) and the other by Monogram Biosciences--closely reflected phenotypically measured viral susceptibility to etravirine in these viral isolates.

A potential treatment for HIV may one day help people who are not responding to Anti-Retroviral Therapy, suggests new research published tomorrow in The Journal of Immunology. Scientists looking at monkeys with the simian form of HIV were able to reduce the virus levels in the blood to undetectable levels, by treating the monkeys with a molecule called D-1mT alongside Anti-Retroviral Therapy (ART).

The Role Brazil has played in changing global AIDS policy and promoting widespread access to AIDS treatment is explored in a new paper by academics from Scotland and the United States. Brazil's large-scale, successful HIV/AIDS treatment program is considered a model for other developing countries aiming to improve access to AIDS treatment.

Immune reconstitution inflammatory syndrome (IRIS) results from pathological immune responses occurring during immune reconstitution. IRIS is best considered a group of disorders with a wide range of clinical manifestations, incorporating disease resulting from pathological inflammation to pathogens, immune-mediated inflammatory disease and autoimmune disease. Clinical effects range from a mild, self-limiting illness to severe morbidity and mortality. Clinicians working in the field of HIV medicine can expect to encounter individuals with IRIS.

The authors report Haemophilus ducreyi genetic material detected by polymerase chain reaction in biopsies of oesophageal lesions in three HIV-1-infected patients. This finding may be an indication of its aetiopathological role in oesophageal lesions of HIV patients.

Hemorrhagic lesions are frequently found on cranial MRI scans in cerebral toxoplasmosis. AIDS patients presenting with hemorrhagic cerebral lesions should be considered for a trial of presumptive antitoxoplasma treatment.

Implications of and perspectives on HIV surveillance using a serological method to measure recent HIV infections in newly diagnosed individuals

Cross-sectional surveillance of recent HIV infections proved to be relevant to the identification of current risks for acquiring HIV infection. The high proportion of recent HIV infections in MSM and the even higher proportion in MSM younger than 30 years indicate ongoing HIV transmission in this group. The method will be used in future national HIV surveillance in Germany.

Vertically acquired HIV diagnosed in adolescence and early adulthood in the United Kingdom and Ireland: findings from national surveillance

A small number of young people with vertically acquired HIV survive childhood without ART and are diagnosed at age >=13 years in the United Kingdom/Ireland. Half of the patients were asymptomatic, highlighting the importance of considering HIV testing for all offspring of HIV-infected women, regardless of age or symptoms. Increased awareness among clinicians and parents is required to reduce delayed presentation with advanced disease and to avoid onward transmission as these young people become sexually active.

Objective amount of limb fat in HIV-infected subjects with subjective diagnosis of lipoatrophy

The diagnosis of lipoatrophy was highly correlated with the amount of limb fat, irrespective of the investigators. HIV-infected men with clinically evident lipoatrophy had a limb fat loss of >50% compared with non-HIV-infected healthy males.

Drug-resistant forms of HIV can be spread between individuals who have not received anti-retroviral treatment, according to Professor Deenan Pillay from University College, London and the Health Protection Agency, speaking at the Society for General Microbiology meeting at Harrogate March 30.

More than 1.7 million people have visited a multi-media webpage urging California Governor Arnold Schwarzenegger to 'Have a Heart' and save 'Positive Healthcare,' a California primary care case management health care plan caring for low income people living with AIDS. The webpage (http://ga1.org/campaign/ahf_gov_haveaheart) is a part of an ambitious ongoing public awareness campaign spearheaded by AIDS Healthcare Foundation (AHF), the operator of the Positive Healthcare program, intended to persuade the Governor and State health officials to halt the forced closure of the respected money-saving AIDS care plan. Without intervention from the Governor or other officials, Positive Healthcare will be forced to cease operating after this Tuesday, March 31st.

Although former President George W. Bush "made an ambitious new commitment to the global fight against AIDS," and Congress in 2008 "authorized billions in new spending," lawmakers and philanthropists "will retreat" as the current economic recession continues, a Providence Journal editorial says. So it "comes as a rare bit of good news" that Phillip Ragon -- founder of the software company InterSystems Corp. -- is "giving $100 million of his own to the quest for an AIDS vaccine," the Journal says. Ragon "will allocate his gift in $10 million annual installments over 10 years" to the newly formed Ragon Institute -- a collaboration between Massachusetts General Hospital, the Massachusetts Institute of Technology and Harvard University -- the Journal continues, adding that the three groups will "join in an effort to find new approaches" to an HIV/AIDS vaccine.

The UK Court of Appeal has ruled that refused asylum seekers should not be classified as normally resident in the UK and are therefore not entitled to free National Health Service (NHS) treatment and care.

PITTSBURGH, March 30 /PRNewswire-FirstCall/ -- Mylan Inc. (NASDAQ:MYL) today announced that Matrix Laboratories Limited, its India-based subsidiary in which it holds a 71.2% controlling interest, has received the first tentative approval from the U.S. Food and Drug Administration (FDA) under the President's Emergency Plan for AIDS Relief (PEPFAR) for its Abbreviated New Drug Application (ANDA) for Emtricitabine and Tenofovir Disoproxil Fumarate Tablets, 200 mg/300 mg.

Cardiovascular Mortality And Shortness Of Breath In Heart Failure Patients With Normal To High Blood Pressure Are Reduced When Relaxin Is Prescribed

A phase II study (PRE-RELAX-AHF), as reported in an article published Online First and in an upcoming edition of The Lancet, coinciding with the announcement of the findings at the American College of Cardiology (ACC) meeting in Florida USA, reveals an improvement of cardiovascular mortality and shortness of breath as well as other clinical end points for heart failure patients with high blood pressure when prescribed the naturally occurring hormone Relaxin.

This study showed that syphilitic hepatitis is common, occurring in 38% (12/32) of HIV-positive patients with early stages of syphilis infection. Most cases occurred during secondary syphilis, with the most common finding being a maculopapular rash. Syphilis should be included in the differential diagnosis of HIV patients presenting with liver test abnormalities, rash and/or sexual risk factors.

Loneliness, social support and family function of people living with HIV/AIDS in Anhui rural area, China

Loneliness prevails among PLWHA. It may limit PLWHA's ability or access to social relationship. These findings support the hypothesis that if PLWHA are better supported and cared for, their negative psychosocial consequences might be prevented or at least reduced.

The authors report this case to highlight the possibility of a delayed hypersensitivity reaction as an important potential side-effect of enfuvirtide treatment. A highly antiretroviral treatment-experienced man was commenced on a new regimen containing enfuvirtide. Prophylaxis for Pneumocystis jirovecii pneumonia was started using trimethoprim/sulphamethoxazole (TMP-STX) simultaneously. Ten days later, he developed a maculopapular rash on the chest and abdomen without any systemic features.

Recurrence of cryptococcal meningitis in HIV-infected patients following immune reconstitution

Two HIV-infected patients had recurrent cryptococcal meningitis (CM) despite treatment with fluconazole and immune reconstitution with combination antiretroviral therapy (CART). Following treatment of CM with fluconazole, lumbar puncture should be performed either after completion of induction treatment for CM or before starting CART, in order to confirm cerebrospinal fluid sterility.

The study indicates that NVP resistance after sdNVP was associated with CD4 cell count at delivery. ZDV-sdNVP regimen was of more significance in the prevention of the emergence of NNRTI-related DR than sdNVP.

Manual isolation method is a cheaper alternative, but because the nucleic acid isolation can be performed in a shorter time by automated systems when compared with manual isolation method, these systems can be preferred especially in the laboratories that have high number of samples.

It was found that this hemolysin induced apoptosis in L929 and HeLa cells as evidenced by microscopic observations and DNA ladder, respectively. Moreover, this hemolysin was shown to possess anti-HIV-1 activity in CEM cell culture.

Reducing Risky Sexual Behavior and Substance Use Among Currently and Formerly Homeless Adults Living With HIV

The authors examined the efficacy of the Healthy Living Program in reducing risky sexual behavior and substance use among adults with HIV infection who were marginally housed (i.e., homeless at some point over a 37-month period). Intensive, skill-focused intervention programs may improve the lives of marginally housed adults living with HIV infection.

The authors also present a hypothesis in relation to HIV-associated delirium as a potential neuropsychiatric manifestation of the immune reconstitution inflammatory syndrome in children commenced on highly active antiretroviral therapy.

A 49-year-old man in the advanced stages of H.I.V. has not told friends about his situation because of the social stigma attached to the disease. "The worst thing for me is the loneliness," he said. Two weeks after this photograph was taken, he died.

BANGKOK — The most heartbreaking moment for doctors and nurses treating people with H.I.V./AIDS in Myanmar is the arrival of a new patient. Running short of funds and medications, clinics have started turning dying people away.

“They continue to knock on our doors, even though we can’t take in most of them,” said Joe Belliveau, operations manager of the international aid group Médecins Sans Frontières.

The likelihood of GlaxoSmithKline’s Cervarix reaching the US market has been given a boost after the company said it has submitted final data from a key study of the cervical cancer vaccine to the Food and Drug Administration.

Liver Steatosis in HIV Positive Patients with and without Hepatitis C Coinfection

Liver steatosis, or accumulation of fat in liver cells -- also called non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) -- has a variety of causes including viral hepatitis, especially with hepatitis C virus (HCV) genotype 3. (The name distinguishes from a similar condition caused by excessive alcohol consumption.) Steatosis may coexist with -- and contribute to -- liver fibrosis, cirrhosis, and hepatocellular carcinoma.

Prevalence and Clearance of Anal Human Papillomavirus (HPV) Infection in HIV Positive Men and Women

Human papillomavirus (HPV) can cause genital warts, and certain "high-risk" types --especially 16 and 18 -- can cause genital, anal, and oral cancers. Although considerable research has shown that HIV positive people are more likely to become infected with HPV and tend to develop more severe disease, studies have yielded conflicting data.

At the 13th International Symposium on Viral Hepatitis and Liver Disease (ISVHLD) last week in Washington, DC, experts in the field of viral hepatitis were asked to present their views on various issues.

Dr. Robert Perrillo of the Hepatology Division at Baylor University Medical Center in Dallas, Texas, presented his opinions concerning how best to utilize the new anti-HBV agents that have recently become available. Following is a summary of his remarks at the meeting.

On March 30, 2009, FDA granted tentative approval for abacavir sulfate and lamivudine tablets, 600 mg / 300 mg, manufactured by Matrix Laboratories Limited of Hyberdad, India, for use in combination with other antiretrovirals in the treatment of HIV infection. The application was reviewed under expedited review provisions for the President's Emergency Plan for AIDS Relief (PEPFAR).

CHINA is facing an epidemic of HIV infection after the government admitted yesterday that new cases had risen by 45pc in two years.

AIDS is now the leading cause of death among infectious diseases on the mainland, as official figures showed that 7,000 people had died in the first nine months of 2008 and 45,000 were infected with HIV.

African Americans, who make up 13 percent of the U.S. population, are disproportionately affected by AIDS, accounting for nearly 49 percent of newly diagnosed HIV/AIDS cases nationwide. About 500,000 African Americans are now living with HIV/AIDS. Yet there are very few African American HIV/AIDS researchers, due to historical, social and other factors that prevent them from training in the biomedical, behavioral and social aspects of HIV/AIDS research.

A heroic shop assistant who was bitten on the hand by a middle-aged woman after he tried to stop her attacking a teenage girl has spoken of his fear of contracting HIV and hepatitis.

Brian Noonan, who was working at the Vivo store in Dolphins Barn, was trying to pull local woman Miriam Power away from the young teen after she attacked her at the counter.

Power (40) from the Seagull House Flats on Crumlin Road, was found guilty of assault after the Richmond Court heard that she had shouted "I'm going to kill you," to her victim before biting Brian on August 3, 2007.

Within a decade, Owensboro could be the production center for a drug that could effectively eliminate the spread of HIV and AIDS worldwide -- if clinical trials are successful.

Kenneth Palmer, a researcher at the Owensboro Cancer Research Program, is the senior author of a study published Monday by the National Academy of Sciences about how the HIV inhibitor can be produced cheaply in plants.

Plans call for the drug -- if it eventually wins approval from the Food and Drug Administration -- to be grown in a form of tobacco plants patented by Kentucky BioProcessing in Owensboro and produced by KBP.

UN Secretary General Ban Ki-moon urged donors to ignore the global economic downturn when it comes to giving to a major international fund to fight AIDS, tuberculosis, and malaria.

"At this time of economic crisis I say to you that spending on AIDS, tuberculosis and malaria is a smart investment, it is a true recovery package," he said in a video message played at the start of a two-day meeting in Spain of key donors to the Global Fund.

"The Global Fund has saved millions of lives and it has shown that we can beat these diseases. It is important that we replenish it," he said, adding it "helps parents, workers and teachers stay alive and productive".

Emerging role of hepatocellular carcinoma among liver-related causes of deaths in HIV-infected patients: The French national Mortalite 2005 study

Longer exposure to hepatitis C (HCV) or B virus (HBV) and the increased use of hepatitis treatment might have an impact on liver-related deaths in patients co-infected with the Human Immunodeficiency Virus (HIV). We describe the proportion of liver-related deaths among HIV-infected patients in 2005 compared with 2000.

Conclusion: Liver-related deaths, mainly liver cancers, have increased in HIV-infected patients in France despite wide access to HCV treatment. The stability of HBV-related deaths might be explained by the use of dually active antiretroviral drugs in co-infected patients.

In a second analysis, this time including 9,155 patients, 24 percent started treatment at CD4 counts of more than 500 cells per millimeter, while the other 76 percent delayed therapy till after their counts fell below that threshold. In this group, patients who deferred therapy experienced a 94 percent rise in death risk compared to those who began their therapy earlier.

"Our study adds to the growing evidence that support earlier initiation of therapy to improve survival," Kitahata said. "We think antiretroviral treatment should be started when the CD4 count is above 500. I feel these data are strong enough that I would start a patient who is ready and willing to begin therapy at a CD4 count above 500 and certainly between 350 and 500," she said.

Dr. Paul E. Sax, from the division of infectious diseases and the department of medicine at Brigham and Women's Hospital in Boston, said the study does seem to tilt the argument in favor of earlier treatment.

Prevention for HIV serodiscordant couples: it's more than just condoms

Promoting 100% condom use may not be the most appropriate HIV prevention strategy for serodiscordant couples, according to research presented to the Fifteenth Conference of the British HIV Association. However, researchers found that there was little awareness or use of other methods of HIV prevention, such as post-exposure prophylaxis (PEP) or the impact of viral load on infectiousness.

TB treatment completion rates for HIV-positive UK patients: good but not quite on target

Just over 80% of HIV-positive patients co-infected with tuberculosis (TB) complete their full course of TB treatment, according to an audit presented to the fifteenth annual conference of the British HIV Association in Liverpool. This rate of treatment completion is below the 85% target set by the UK’s Chief Medical Officer. The vast majority of patients, however, received treatment with a standard and recommended regimen of tuberculosis drugs.

Women living with HIV in the UK would welcome greater provision of integrated sexual and reproductive healthcare services by their HIV clinics, according to three separate studies presented at the British HIV Association conference in Liverpool this week. There is a particular need for advice on conception and contraception that reflects the specific issues for women living with HIV.

Delegates at the British HIV Association conference in Liverpool this week presented the findings of pilot projects that helped increase the uptake of HIV testing, highlighted the continuing problem of the untested children of HIV-positive parents, and identified a limited awareness of HIV testing guidelines among non-HIV doctors.

Today, during the 87th General Session of the International Association for Dental Research, convening at the Miami Beach Convention Center, a group of scientists from Nihon University (Tokyo, Japan) will present findings suggesting that periodontal disease could act as a risk factor for reactivating latent HIV-1 in affected individuals. Latently infected cells harbor HIV-1 proviral DNA genomes integrated with heterochromatins, allowing for the persistence of transcriptionally silent proviruses. Hypoacetylation of histone proteins by histone deacetylases (HDACs) is primarily involved in the maintenance of HIV-1 latency by repressing transcription from HIV-1 provirus. On the other hand, periodontal diseases, caused by infection with the bacterium Porphyromonas gingivalis (P. gingivalis), are found worldwide and are among the most prevalent microbial diseases of mankind.

Lower CD4 Counts in Seroconverters Suggest HIV May Have Become More Virulent

There is no clear answer yet to the question of whether or not HIV seroconverters have presented with progressively lower CD4 cell counts over the course of the HIV epidemic. Lower CD4 counts might indicate that the virus is becoming more virulent, or able to replicate and infect new cells more rapidly and efficiently.

Fosamprenavir (Lexiva) Works Well with 100 mg Ritonavir (Norvir) at 96 Weeks in Treatment-naive Patients

The use of ritonavir (Norvir) to boost blood levels of other protease inhibitors has improved the effectiveness and convenience of combination antiretroviral therapy, but ritonavir can cause metabolic side effects and adds to the number of pills a patient must take.

Non-Hodgkin Lymphoma Mortality Remains High for People with HIV, but Antiretroviral Therapy Reduces Risk

Non-Hodgkin lymphoma (NHL), one of the 3 AIDS-defining malignancies, remains a significant cause of death among HIV positive individuals in the HAART era. But effective antiretroviral therapy (ART) significantly reduces the risk of NHL, and blood biomarkers can predict its development, according to studies presented at the recent 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009) in Montreal.

FDA Approves Generic Versions of Abacavir/lamivudine, Tenofovir/emtricitabine, Nevirapine, and Stavudine/lamivudine/nevirapine for PEPFAR Program

Drug cost remains a major barrier to access to antiretroviral therapy in resource-limited areas. Several companies produce generic versions of anti-HIV medications under World Trade Organization provisions for low- and middle-income countries.

Tuberculosis characteristics and incidence were assessed among patients with concurrent human immunodeficiency virus infection and chronic hepatitis C virus infection who were receiving interferon-based therapy at 3 hospitals in Spain. Four of 570 patients received a diagnosis of tuberculosis; all of them presented with a decrease in CD4+ cell count before diagnosis, and 3 of them received a delayed diagnosis. After tuberculosis treatment, all patients were cured.

Safety, Tolerability and Effectiveness of Generic HAART in HIV-Infected Children in South India

The most common adverse events to therapy were nausea and rash. Over one-fifth of patients substituted therapy due to toxicities and 19.4% of patients switched to second-line protease inhibitor-containing regimens. In this South Indian pediatric cohort, generic HAART was safe, effective and relatively well tolerated.

The method described here is capable of accurately determining the worldwide occurrence and subtype distribution of any crystallographically resolved HIV-1 epitope recognized by a neutralizing antibody, which could be useful for multivalent vaccine design. More importantly, these calculations demonstrate that globally relevant, structurally conserved epitopes are present in the sequence variable V3 loop.

Analysis of antiretroviral drug-resistance mutations in protease and reverse transcriptase from this untreated population showed a low level of specific mutations. These mutations were associated with subtype polymorphism rather than with resistance to antiretroviral drugs. The wide diversity and the emergence of recombinant strains are in accordance with the rapid spread of new HIV strains in the population and, thus, the dynamic evolution of the epidemic.

Lack of a Decline in HIV Incidence in a Rural Community with High HIV Prevalence in South Africa, 2003–2007

The authors show for the first time that high levels of HIV incidence have been maintained without any sign of decline over the past 5 years in both women and men in a rural South African community with high HIV prevalence. It is unlikely that the HIV epidemic in rural South Africa can be reversed without new or intensified efforts to prevent HIV infection.

Dendritic Cell Differentiation and Maturation in the Presence of HIV Type 2 Envelope

HIV-2 Env had no effects upon DC differentiation and maturation despite its broad receptor usage and ability to modulate monocyte function. It is plausible to speculate that a reduced ability of the HIV-2 Env to impair myeloid DC function could represent a contributory factor to the relatively benign course of HIV-2 disease.

Morbidity and mortality among a cohort of HIV-infected adults in a programme for community home-based care, in the Kilimanjaro Region of Tanzania (2003-2005)

The high level of morbidity observed in this study, and the causes of mortality that were identified, emphasise the need for CHBC programmes to provide HIV-infected patients with improved access to basic resources such as SXT and isoniazid prophylaxis, clean water, oral rehydration therapy, and micronutrient supplementation, in addition to increased access to ART.

HIV superinfection may cause increasing viral loads and a second seroconversion illness

Infection with a second strain of HIV (superinfection) may have medical consequences, according to a presentation at the 15th British HIV Association (BHIVA) conference.

A small study of eight gay men with HIV who were not on treatment and had increases in their viral load found two whose viral load increases were clearly due to infections with a second strain of HIV.

In one case the patient‘s second strain of HIV was drug-resistant. He also experienced a recurrence of acute HIV symptoms which required hospitalisation for suspected meningitis and a large, though temporary decrease in CD4 count. In the other case the patient’s original strain of HIV, which was drug-resistant, was replaced by an apparently stronger non-resistant strain and his viral load increased from around 3000 to half a million. However he maintained a CD4 count over 1000 and his viral load had returned to 3000 a year later.

Mental impairment relatively more common in younger people with HIV: brain changes seen but significance unclear

Several presentations at the 15th British HIV Association (BHIVA) conference in Liverpool found further evidence that even people on stable HIV therapy and with good CD4 counts show signs of subtle psychological and neurological impairment, and one study found signs of nerve cell loss in the brain. However in most of the studies the differences in performance were subtle, and in the study that found brain changes, they were not related to test results.

London patient surveys find widely different rates of patients referred to care and lost to follow-up

A number of surveys presented to the 15th British HIV Association (BHIVA) conference in Liverpool have found wide variation between clinics in the proportion of patients in the UK who see an HIV doctor within two weeks of diagnosis and also the number who disappear from care (in medical terms ‘lost to follow-up’ or LTFU).

The London Centre for Nanotechnology will develop a new device to enable people living with HIV to monitor their own health and the effectiveness of their treatments, thanks to a £2 million EPSRC (Engineering and Physical Sciences Research Council) grant announced today.

Correlates of Incarceration Among Young Methamphetamine Users in Chiang Mai, Thailand

Incarcerated methamphetamine users are engaging in behaviors and being exposed to environments that put them at increased risk of infection and harmful practices. Alternatives to incarceration need to be explored for youths.

Factors Associated With the Sexual Behavior of Canadian Aboriginal Young People and Their Implications for Health Promotion

Sexual behavior change interventions for Aboriginal young people must move beyond the individual and incorporate interpersonal and structural dimensions. Interventions to reduce substance use and sexual abuse and promote feelings of family connectedness in this population should be explored. Young people living on land reserves need special attention.

The Effect of Name-Based Reporting and Partner Notification on HIV Testing in New York State

HIV reporting has permitted improved monitoring of New York’s HIV/AIDS epidemic. This benefit has not been offset by decreases in HIV testing behavior, including willingness to test among those at high risk of acquiring HIV.

Comfort with HIV testing was associated with higher HIV knowledge. Approximately half of the respondents indicated that HIV tests are different from other tests and that women need more information prior to testing. Results demonstrated clear consensus in support of routine testing. Increased efforts to disseminate resources to providers coupled with providers' effective communication of information to pregnant women can build on the support that women have conveyed for HIV testing during pregnancy.

Single Nef Proteins from HIV Type 1 Subtypes C and F Fail to Upregulate Invariant Chain Cell Surface Expression But Are Active for Other Functions

The authors identified two primary HIV-1 NefC and NefF alleles that are selectively impaired for Ii upregulation and that may help to elucidate the mechanism of this Nef function in the future. It will be important to determine whether the observed differences are HIV-1 subtype dependent and influence viral immunopathogenesis.

Damage to patients’ immune systems is happening sooner now than it did at the beginning of the HIV epidemic, suggesting the virus has become more virulent, according to a new study in the May 1, 2009 issue of Clinical Infectious Diseases, now available online.

Darunavir: A Review of its Use in the Management of HIV Infection in Adults

Darunavir is an oral nonpeptidic HIV-1 protease inhibitor (PI) that is used, together with a low boosting dose of ritonavir, as part of an antiretroviral therapy (ART) regimen in treatment-experienced and -naive patients with HIV-1 infection.

Maraviroc: A coreceptor CCR5 antagonist for management of HIV infection

Available data support the use of maraviroc, the first CCR5 antagonist to receive FDA marketing approval, as part of an optimized antiretroviral regimen in treatment-experienced patients infected with CCR5-tropic HIV.

Lamivudine (CAS 134678-17-4) is a synthetic nucleoside analogue with activity against HIV-1 and HBV. Stavudine (CAS 3056-17-5) is a synthetic thymidine nucleoside analogue, active against the human immunodeficiency virus (HIV). Lamivudine and stavudine in combination with other antiretroviral (ARV) agents are indicated for the treatment of HIV infection. As there are no suitable pediatric ARVs, adult fixed-dose ARVs are commonly used in children. This practice poses concerns about dose inaccuracy, which may lead to resistance or toxicity. A new fixed-dose combination (FDC) tablet for oral suspension, containing lamivudine 40 mg and stavudine 10 mg has been developed. An open-label, balanced, randomised, two-treatment, two-period, two-sequence, single-dose, crossover bioequivalence study was conducted following administration of a fixed-dose combination of lamivudine and stavudine tablet for oral suspension (test formulation) and innovator products (reference formulations) in healthy, adult, male human subjects under fasting condition.

The isothiocyanate sulforaphane [SF; 1-isothiocyanato-4(R)-methylsulfinylbutane] is abundant in broccoli sprouts in the form of its glucosinolate precursor (glucoraphanin). SF is powerfully bactericidal against Helicobacter pylori infections, which are strongly associated with the worldwide pandemic of gastric cancer. Oral treatment with SF-rich broccoli sprouts of C57BL/6 female mice infected with H. pylori Sydney strain 1 and maintained on a high-salt (7.5% NaCl) diet reduced gastric bacterial colonization, attenuated mucosal expression of tumor necrosis factor-{alpha} and interleukin-1ß, mitigated corpus inflammation, and prevented expression of high salt-induced gastric corpus atrophy. This therapeutic effect was not observed in mice in which the nrf2 gene was deleted, strongly implicating the important role of Nrf2-dependent antioxidant and anti-inflammatory proteins in SF-dependent protection. Forty-eight H. pylori-infected patients were randomly assigned to feeding of broccoli sprouts (70 g/d; containing 420 µmol of SF precursor) for 8 weeks or to consumption of an equal weight of alfalfa sprouts (not containing SF) as placebo. Intervention with broccoli sprouts, but not with placebo, decreased the levels of urease measured by the urea breath test and H. pylori stool antigen (both biomarkers of H. pylori colonization) and serum pepsinogens I and II (biomarkers of gastric inflammation). Values recovered to their original levels 2 months after treatment was discontinued. Daily intake of sulforaphane-rich broccoli sprouts for 2 months reduces H. pylori colonization in mice and improves the sequelae of infection in infected mice and in humans. This treatment seems to enhance chemoprotection of the gastric mucosa against H. pylori-induced oxidative stress.

A new analytical technique is helping scientists learn how organisms as simple as seaweed can mount complex chemical defenses to protect themselves from microbial threats such as fungus. Known as desorption electrospray ionization mass spectrometry (DESI-MS), the technique for the first time allows researchers to study unique chemical activity taking place on the surfaces of these organisms.

The Miami Herald on Monday examined issues that some HIV-positive men who have sex with men face when determining when to reveal their status to potential partners. According to the Herald, a recent study from the Gay Men's Health Crisis found that half of U.S. residents surveyed said they believe that HIV/AIDS contributes to discrimination against MSM. In addition, discrimination in the MSM community toward HIV-positive MSM is not discussed widely, according to the Herald. This stigma often leads to a fear of disclosure among HIV-positive MSM, which can contribute to high-risk sexual activity and the spread of HIV.

Obama Administration Announces New Campaign To Refocus National Attention On The HIV Crisis In America

Every 9 ½ minutes another person in America becomes infected with HIV. Officials from the White House, Department of Health and Human Services and the Centers for Disease Control and Prevention (CDC) announced today a new five-year national communication campaign, Act Against AIDS, which highlights this alarming statistic and aims to combat complacency about the HIV/AIDS crisis in the United States.

The Hamilton Spectator on Monday examined debate among some legal experts and HIV/AIDS advocates over criminalizing HIV transmission for those who know they are living with the virus. The Spectator examined the case of Johnson Aziga, an HIV-positive Canadian resident who on Saturday was convicted of murder for not informing sexual partners of his HIV status and knowingly spreading the virus. One of Aziga's sexual partners who became contracted the virus died. According to the Spectator, although some people believe that knowingly spreading HIV should be considered a criminal act, many HIV/AIDS advocates contend that such actions are unreasonable and counterproductive.

Inter Press Service last week examined how researchers are investigating the use of antiretroviral drugs as a possible method of pre-exposure prophylaxis. AIDS Vaccine Advocacy Coalition's Executive Director Mitchell Warren recently said that such efforts are "a pivotal moment in HIV/AIDS research." Mitchell -- who was speaking at the Fourth South African AIDS Conference -- said, "We are at a time where prevention and treatment need to marry." Salim Abdool Karim, director of the Centre for the AIDS Program of Research in South Africa, said that PrEP is "biologically plausible" and that the method "could prevent millions of new infections every year."

Mylan Inc. announced that Matrix Laboratories Limited, its India-based subsidiary in which it holds a 71.2% controlling interest, has received the first tentative approval from the U.S. Food and Drug Administration (FDA) under the President's Emergency Plan for AIDS Relief (PEPFAR) for its Abbreviated New Drug Application (ANDA) for Emtricitabine and Tenofovir Disoproxil Fumarate Tablets, 200 mg/300 mg.

According to a new report, PEPFAR, President Bush's AIDS treatment program reduced the total number of AID/HIV deaths by 1.2 million from 2004 to 2007. PEPFAR (President's Emergency Plan for AIDS Relief) targeted Africa's most stricken countries.

PEPFAR was launched by President Bush in 2003. Experts from the Stanford University, lead by Eran Bendavid, state in a report published in the Annals of Internal Medicine that the program reduced AIDS deaths by approximately 10.5% per year in the most stricken African countries. They added that PEPFAR did not prevent new infections or reduce overall prevalence of AIDS.

A Canadian man who is thought to have recklessly transmitted HIV to seven women, two of whom subsequently died, has made legal history by becoming the first person ever to be convicted of first-degree murder for sexual HIV transmission. The case has reignited the criminalisation debate in Canada, which has prosecuted more HIV-positive individuals per capita for sexual HIV exposure or transmission than any other country in the world.

Over 50% of tuberculosis (TB) patients in London were not offered an HIV test, investigators reported at the Fifteenth Annual Conference of the British HIV Association. Even in groups with a high risk of HIV, the offer of a test for HIV was not universal, the conference was told.

A separate audit of TB treatment for patients with diagnosed HIV was presented to the conference and found that the proportion of patients completing treatment was slightly below target.

Early KS can be successfully treated with HIV treatment with no need for chemotherapy

The early stages of the AIDS-defining cancer Kaposi’s sarcoma (KS) can be successfully treated with HIV drugs alone without the need for additional chemotherapy, research presented to the Fifteenth Annual Conference of the British HIV Association showed.

Many Non-specialist Hospital Physicians Have a Poor Understanding of Antiretroviral Therapy for HIV

The mean percentage of correct responses was 33% for resident physicians and 37% for attending physicians, compared with 93% for ID or HIV specialists. In particular, non-ID/HIV physicians scored less than 6% on questions about antiretroviral drug dosing. Higher scores were independently associated with ID or HIV specialty, number of outpatients seen per month, and reported comfort level in managing HIV patients (all P < 0.001).

The question of what is the optimal timing for initiating antiretroviral therapy (ART) in asymptomatic HIV positive individuals has been controversial for more than a decade. Current U.S. and European guidelines recommend treatment for asymptomatic HIV patients who have a CD4 count less than 350 cells/mm3 (1).

However, results of a new study, published April 1, 2009 in the advance online edition of the New England Journal of Medicine, add weight to a growing body of evidence suggesting that earlier treatment initiation can reduce the risk of various conditions and prolong survival among HIV patients.

Non-AIDS-defining Cancer Is an Increasingly Common Cause of Death among HIV Patients

Antiretroviral therapy (ART) has dramatically reduced overall mortality among people with HIV, especially deaths related to opportunistic illnesses. As HIV positive people survive longer, however, they are more prone to progressive diseases that develop over time, including liver disease and non-AIDS-defining cancers.

HBV is unusual in that it uses reverse transcriptase to replicate, a characteristic usually seen only in retroviruses such as HIV. Several nucleotide/nucleoside analog inhibitors are approved for the treatment of chronic hepatitis B virus (HBV) infection -- lamivudine (Epivir-HBV), adefovir (Hepsera), entecavir (Baraclude), telbivudine (Tyzeka), and tenofovir (Viread) -- and some are dually active against both HBV and HIV.

ISVHLD: Studies Shed More Light on Acute Hepatitis C among HIV Positive Men in the U.S. and Europe

Since around 2000, clinicians have been reporting outbreaks of apparently sexually transmitted acute hepatitis C virus (HCV) infection among mostly HIV positive men in cities in the U.K. and continental Europe. More recently, such cases have also been described in Australia and the U.S., and one group has found that HCV infection in people who already have HIV may lead to unusually rapid liver disease progression.

Outlining a bold set of initiatives that would increase the role of government well beyond the boundaries sketched out by the $787 billion economic stimulus package, President Barack Obama has proposed a 2010 budget supporting his commitment to expanding a range of domestic programs, redistributing wealth to middle- and lower-income families, and reforming the health care system. The spending plan is breathtaking in scope and is designed to replace conservative policies that have been embraced by Republican administrations going back to Ronald Reagan. Released on February 26, the $3.6 trillion proposal calls on Congress to commit to a down payment of $630 billion over the next decade to finance health care reform and work with the administration to design a reform package. The budget adds substantially to the $150 billion in health-related revenues from the economic stimulus package that Obama signed into law on February 17.

If left untreated, HIV infection inevitably degrades the immune system, leading to the development of life-threatening infections-AIDS-about 10 years later. The time between initial HIV infection and the development of AIDS is commonly referred to as the symptom-free, or asymptomatic, period. The reason for this is that during that time life-threatening infections are uncommon. The idea of dividing the stages of HIV disease into these specific periods occurred early in the course of the AIDS pandemic, when the medical focus was on delaying the appearance of severe infections and the always-looming spectre of death.

For some participants, regardless of CD4+ counts, these symptoms were intense.

Some of the above-listed symptoms could occur as isolated problems or as part of many other health conditions, including but not limited to anxiety, depression and hormonal deficiencies. Although none of the study participants were experiencing life-threatening conditions, even those who had more than 350 CD4+ cells were experiencing symptoms of illness, perhaps unrelated to HIV.

The international study team suggests that doctors and nurses carefully interview their patients about health-related issues regardless of CD4+ counts. In doing so, health care professionals may uncover underlying conditions that are reducing their patients’ quality of life, which would allow them to provide relief.

A SMALL fraction of Ugandans have been able to naturally knock off HIV from their body, a development that could lead to an HIV vaccine, scientists have said.

Dr. Pontiano Kaleebu, an immunologist heading the Basic Sciences Programme of the MRC/UVRI Uganda Research Unit on AIDS at the Uganda Virus Research Institute (UVRI), told Saturday Vision that an ongoing study and a previous one at the institute had unearthed signs that some Ugandans may be resistant to HIV.

They have special white blood cells that can only be produced when the virus attacks the body. However, even with the most sophisticated tests, HIV could not be found in these individuals, implying that the virus had tried to infect them but the immune system kicked it out.

The news that a small number of Ugandans are possibly resistant to HIV is exciting but calls for extreme caution.

While it raises hopes of getting a vaccine, the revelation does not have any immediate application to the lives of Ugandans. What scientists at the Uganda Virus Research Institute have established in collaboration with American and British researchers is that some individuals in Uganda have evidence that they have ever been exposed to HIV but were not infected. The scientists have not yet got conclusive evidence that these individuals can never be infected by HIV. Even then, such people can only be very few in society.

HIV-Positive Patients Show Lower Response to Hepatitis B Vaccination Even at Double Doses: Presented at BHIVA

LIVERPOOL, United Kingdom -- April 7, 2009 -- Individuals who are HIV-positive (+) have a reduced response to the intramuscular hepatitis B virus (HBV) vaccine (Engerix) compared with HIV-negative (-) vaccine recipients, even when a double dose of the vaccine is given, according to a study presented here at the 15th Annual Conference of the British HIV Association (BHIVA).

A leading new tuberculosis vaccine, called MVA85A, has been found to be safe in its Phase I trial.

Lead researcher Dr. Helen McShane, reader in vaccinology and Wellcome senior fellow at the University of Oxford's Jenner Institute in England, studied the effects of the vaccine specifically in people who had latent tuberculosis infection (LTBI), which can cause full-blown disease when re-activated.

Note (John2038)This news can be found in reputable meds website such as elsevier, but their access isn't free for all.

Health Minister Ross Wiseman says he is confident Eastern Health 'will make a commitment to provide some kind of continuity' at the HIV-AIDS clinic. (CBC)

Patients who rely on the only HIV/AIDS clinic in Newfoundland and Labrador have been delivered another blow, as the lone nurse-practitioner at the St. John's-based clinic has resigned.

The nurse, who had been on a leave of absence, has decided not to return to her job. She had been responsible for seeing patients after the only infectious diseases specialist in the province moved away.

The clinic was force to close temporarily while the nurse-practitioner, who had the authority to write prescriptions, went on sick leave.

Jones, who said she was told of the resignation on Tuesday afternoon, said the resignation makes a bad situation worse.

Older HIV-positive individuals with neurocognitive impairment or drug problems are at increased risk of suboptimal adherence to medication. Likewise, older adults may be especially vulnerable to immunological and neurocognitive dysfunction under conditions of suboptimal HAART adherence. These findings highlight the importance of optimizing medication adherence rates and evaluating neurocognition in the growing population of older HIV-infected patients.

The Implications of Relationship Fluidity for Condom Use Among Female Sex Workers in Antananarivo, Madagascar

Condom use was less likely in forms in which the distinction between client and lover (sipa in Malagasy) was fluid. For many sex workers, therefore, relationships they understood to be intimate imparted the greatest health vulnerability. It is important to examine the influence of the meaning of sexual relationships on condom use for HIV prevention. Policy implications for HIV prevention for HIV prevention work with sex workers are considered.

Progress in prevention of mother-to-child transmission of HIV infection in Ukraine: results from a birth cohort study

There have been substantial improvements in use of PMTCT interventions in Ukraine, including earlier diagnosis of HIV-infected pregnant women and increasing coverage with antiretroviral prophylaxis and the initial MTCT rate has more than halved. Future research should focus on hard-to-reach populations such as IDU and on missed opportunities for further reducing the MTCT rate.

Plasmablastic lymphoma is a rare variant of a diffuse, large B-cell lymphoma, which typically presents in the oral cavity in immunocompromised patients. In HIV positive patients, this tumor has a tendency to manifest in extramedullary sites. In this report, the authors document a rare instance in which this neoplasm besides affecting the bone marrow also involved the lung. In addition, the lymphoma in the case disclosed CD10 positivity on immunohistochemistry and t translocation on cytogenetic analysis, mimicking a Burkitt/atypical Burkitt lymphoma.

HIV Stigma and Missed Medications in HIV-Positive People in Five African Countries

This study provides evidence of a significant and stable correlation that documents the relationship between perceived HIV stigma and self-reported reasons for missed medications over time. These findings suggest that part of the reason for poor adherence to ARV medications is linked to the stigma experienced by people living with HIV.

Some samples had other mutations selected by these drugs including T97A, and some had amino acid polymorphisms at positions associated with raltegravir and elvitegravir resistance. Mutations associated with other investigational HIV IN inhibitors were also identified. This suggests that HIV strains may vary in their natural susceptibility to HIV IN inhibitors.

The case highlights that coadministration of a PI and tacrolimus is feasible through intense reduction in dose and prolongation of the dosing interval of the calcineurin inhibitor. Complex drug interactions may become more frequent because more HIV-infected patients are undergoing transplantation and newer HIV drugs are being used. Close monitoring and excellent adherence are mandatory to avoid the risk of harm for the graft and patient.

The results suggest that 350 cells per (mu)L should be the minimum threshold for initiation of antiretroviral therapy, and should help to guide physicians and patients in deciding when to start treatment.

An HIV-positive subject who received a bone marrow transplant for leukemia showed no evidence of the virus in his bloodstream after 20 months of follow-up, according to a report by Gero H|[uuml]|tter et al.. In a rare and lucky match-up, his donor was not only compatible but also homozygous for mutations in the HIV receptor CCR5 that result in resistance to HIV infection.

The incidence of Kaposi's sarcoma is increasing amongst Black South Africans and is a growing health problem that requires urgent attention, according to work published by the University of Kwazulu Natal at the 4th South African AIDS Conference in Durban.

Dried blood spots can be used to measure HIV viral load, using the Abbott RealTime HIV-1 assay, although they tend to produce somewhat higher values than viral load tests in plasma, and the method may fail to quantify the virus in some specimens from subjects with low plasma viral loads, according to South African and international studies described at the Fourth South African AIDS Conference in Durban.

Children in rural South Africa may be at increased risk of acquiring MDR-TB in hospitals

Children may be at risk of acquiring multidrug-resistant TB in hospitals in South Africa and more resources should be directed at preventing and controlling infection spread in hospitals, according to research published at the Fourth South African AIDS Conference in Durban.

Portuguese scientists discovered a new molecular mechanism that allows gamma herpes viruses to chronically infect patients and helps to explain why these patients present an abnormally high incidence of the lymphocyte (or white blood cell) cancer lymphoma, particularly when their immune system is compromised.

In conclusion, low serum 25(OH)D concentrations are very common in the elderly. Bone health and physical performance in older persons are likely to improve when serum 25(OH)D is raised over at least 50-60 nmol/liter. The implication for our older population is that at least 64% should receive vitamin D supplements because they had a serum 25(OH)D level lower than 60 nmol/liter.

The Relationship Between Prolonged Antiretroviral Therapy and Cryptogenic Liver Disease

We defined CLD as persistently elevated hepatic transaminase levels in the absence of replicative HBV or HCV infection or other common causes of chronic liver diseaseOur study does not confirm an association between the development of CLD and the prolonged use of antiretroviral drugs.

Gilead Sciences today announced receipt of a Paragraph IV Certification Notice Letter advising that Teva Pharmaceuticals submitted an Abbreviated New Drug Application (ANDA) to the U.S. Food and Drug Administration (FDA) requesting permission to manufacture and market a generic version of Atripla(R) (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg). Atripla is currently sold in the United States through a joint venture between Bristol-Myers Squibb and Gilead.

AIDS Healthcare Foundation (AHF), the largest non-profit HIV/AIDS organization in the US which currently provides medical care and services to more than 100,000 individuals in 21 countries worldwide in the US, Africa, Latin America/Caribbean and Asia, expressed its deep disappointment today regarding President Obama's proposal to spend $45 million over the next five years---only $9 million per year---on a national communications campaign on HIV/AIDS here in the United States. The proposal---Obama's first official action on AIDS---falls far short of the need to adequately address the growing domestic epidemic and appears to be window dressing of a potentially politically-charged issue. The White House will partner with the Department of Health and Human Services (DHHS) and the Centers for Disease Control and Prevention (CDC) in the campaign, the first federally funded national domestic HIV/AIDS campaign in almost twenty years according to White House officials.

An estimated 650 million people, or 10% of the world’s population, have a disability. Although people with disabilities are found within the populations at higher risk of exposure to HIV, not much attention has been paid to the relationship between HIV and disability.

Variable Impact on Mortality of AIDS-Defining Events Diagnosed during Combination Antiretroviral Therapy: Not All AIDS-Defining Conditions Are Created Equal

In the combination antiretroviral therapy era, mortality rates subsequent to an ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in clinical end point trials, prognostic studies, and patient management.

A novel HIV-1 restriction factor that is biologically distinct from APOBEC3 cytidine deaminases in a human T cell line CEM.NKR

The results not only demonstrate that all these aforementioned anti-HIV APOBEC3 proteins do not contribute to this HIV-1 restriction, but also shed light on a novel and potent HIV-1 inhibitor in CEM.NKR cells.

HIV post-exposure prophylaxis in children and adolescents presenting for reported sexual assault

Results indicate that the prevalence of HIV infection among sexually abused children in this population is low, and follow-up rates are poor. Intensive efforts to try to ensure follow-up are warranted whenever PEP is prescribed.

Effect of Highly Active Antiretroviral Therapy on Incident AIDS Using Calendar Period as an Instrumental Variable

Weighting by the inverse probability of calendar period given age at seroconversion, race/ethnicity, and time since seroconversion did not appreciably alter the results. These methods may help resolve discrepancies between observational and randomized evidence.

Association of HIV-Specific and Total CD8+ T Memory Phenotypes in Subtype C HIV-1 Infection with Viral Set Point

The proportions of memory subsets significantly correlated with CD38+CD8+ T cells. Thus, it is likely that a high Ag burden resulting in generalized immune activation may drive differentiation of HIV-specific and total memory CD8+ T cells.

The findings suggest that iron and iron-related proteins might be promising candidate urine biomarkers to identify HIV-infected children at risk of developing HIVAN and HIV-HUS. Moreover, based on the results of previous studies, the authors speculate that the release or accumulation of iron in the kidney of HIV-infected children may contribute to the rapid progression of their renal disease, and could become a new therapeutic target against HIVAN and HIV-HUS.

Teens in South Africa have found a new use for efavirenz (brand name Stocrin in South Africa and Sustiva in the U.S.), an antiretroviral drug that prevents HIV from making copies of itself in the body. Instead of using efavirenz as it was intended – to keep the AIDS virus at bay – kids are crushing the pills and smoking the powder to get high, ABC News reports.

This study demonstrates that in the general population, albuminuria is associated with renal risk: The higher the level of albuminuria, the higher the risk for need for RRT and the more rapid the rate of renal function decline. Screening for increased albuminuria levels in the general population detects more than half of the patients who started RRT during follow-up, approximately 40% of whom were previously not known to have renal disease. Restricting screening to those with known hypertension, known diabetes, CVD history, or age >55 yr would identify nearly all incident cases of RRT during follow-up; however, nearly half of the individuals with UAC =20 mg/L would be left undetected, but these individuals are at considerable cardiovascular and renal risk.

Gilead Sciences today announced that DAR-311 (DORADO), a Phase III clinical trial evaluating the company's endothelin receptor antagonist (ERA) darusentan for the treatment of resistant hypertension, met its co-primary efficacy endpoints of change from baseline to week 14 in trough sitting systolic blood pressure (SBP) and trough sitting diastolic blood pressure (DBP). DORADO is one of two ongoing Phase III clinical trials evaluating the safety, efficacy and tolerability of darusentan as an add-on treatment for resistant hypertension, defined as the failure to achieve goal blood pressure while adhering to full doses of an appropriate three-drug regimen that includes a diuretic. The second study, DAR-312 (DORADO-AC), is approximately 90 percent enrolled and is expected to be completed by the end of 2009.

At the 15th British HIV Association Meeting (BHIVA 2009) held April 1-3, 2009 in Liverpool, UK, researchers reported on a study of treatment-naive HIV patients receiving either lopinavir/ritonavir (Kaletra) in combination with the integrase inhibitor raltegravir (Isentress) or lopinavir/ritonavir plus tenofovir/emtricitabine (Truvada).

The results showed that through 8 weeks of treatment, patients using raltegravir plus lopinavir/ritonavir experienced a significantly greater reduction in viral load than those receiving lopinavir/ritonavir plus tenofovir/emtricitabine, according to the investigators.

Durable Effects of Polylactic Acid for Facial Lipoatrophy in People with HIV

Facial lipoatrophy (loss of fat in the face) is a constant reminder to affected HIV positive individuals that they have a devastating disease. The chief characteristics of facial lipoatrophy are sinking of the cheeks, eyes, and temples, due to loss on subcutaneous fat.

Currently there are 2 temporarily successful interventions for facial lipoatrophy: plastic surgery or the use of fillers. One of several filler components available, polylactic acid (PLA) is called "New Fill" in Europe and "Sculptra" in the U.S. (produced by Dermik Laboratories in Berwyn, PA, a division of Aventis in trasbourg, France).

Two New Studies Suggest an Intensive Disease Management Approach to Smoking Cessation

According to two new studies being published in the April 7 issue of Annals of Internal Medicine, physicians should treat smoking as a chronic disease if they want to help their patients quit successfully. Patients may require repeated or intensive interventions that include pharmacotherapy and counseling, as well as continued dialogue with their physicians.

Changes in Body Composition with Ritonavir-Boosted and Unboosted Atazanavir Treatment in Combination with Lamivudine and Stavudine: A 96-Week Randomized, Controlled Study

This 96-week, open-label, randomized study assessed changes in body composition in treatment-naive patients infected with human immunodeficiency virus type 1 who were treated with either atazanavir or ritonavir-boosted atazanavir, in combination with stavudine and lamivudine. Both treatment groups had similar increases in trunk fat, but patients treated with ritonavir-boosted atazanavir had a significantly lower incidence of lipoatrophy.

Performance of Tests for Latent Tuberculosis in Different Groups of Immunocompromised Patients

Blood tests identified significantly more patients as being infected with M. tuberculosisthan did the skin test, although diagnostic agreement variedacross groups. Based on these results, the authors recommendtailoring applications of the new blood interferon-gamma assays for latent tuberculosis infection in different high-risk groups and advise caution in their current use in immunosuppressed patients.

The HIV-1 load can accurately be quantified by testing DBS by either the Nuclisens or the m2000rt test, although the Nuclisens test may outperform the m2000rt test when nucleic acids are extracted manually.

Cardiovascular prevention is required in more than one half of HIV-infected/treated patients to achieve a reliable effectiveness of modern antiretroviral therapy. As the prognosis of HIV patients improves continuously, this rate is also likely to increase in the future.

Outcomes of human immunodeficiency virus–infected and –exposed children undergoing surgery

Human immunodeficiency virus–positive and –exposed patients present a unique challenge in management which is complicated by concomitant disease and poor nutrition. These patients require an expanded differential diagnosis. The authors believe that, although on the surface there may be a higher complication rate, this needs to be confirmed in an expanded comparative cohort study, which is underway and that patients should still receive the benefit of full surgical intervention.

A Qualitative Study on the Disclosure of Their Condition by Human Immunodeficiency Virus–Positive Adolescents

The health care team should systematically address the issue of disclosure with the adolescent and his family, the aim being to balance the right of the adolescent and that adolescent's family to maintain privacy against the concerns of sexual partners, as well as the adolescent's interest in divulging HIV status to relatives, school staff, and friends.

The current review reveals a robust relationship between adverse psychosocial factors and HIV disease progression. Furthermore, there would appear to be some evidence for particular psychosocial factors to be most strongly associated with HIV disease progression.

After an in-depth, national search, a leading researcher in the design of next-generation vaccines for HIV and influenza has been chosen as the new chair of the Department of Microbiology & Immunology at the University of Rochester Medical Center. The appointment will be effective July 1, 2009, pending approval by the University Trustees.

Tobira Therapeutics Inc. Initiates Proof of Concept Study with TAK-652 for the Treatment of HIV: New phase 2a trial for CCR5 antagonist

PRINCETON, N.J. and SAN DIEGO, April 9 /PRNewswire/ -- Tobira Therapeutics Inc., a clinical stage biotechnology company committed to the research and product discovery against life-threatening and life-altering infectious diseases, today announced that it has initiated a proof-of-concept study for TAK-652, a CCR5 antagonist, in HIV-infected, antiretroviral therapy-experienced, CCR5-naive patients. The study is being conducted under an investigational new drug (IND) application filed with the U.S. Food and Drug Administration (FDA).

South Africa has the most extensive antiretroviral treatment programme in the world -- but experts in the field are warning that it is failing and could soon collapse.

Aids activist and deputy chairperson of the South African National Aids Council Mark Heywood said the 2009-10 budget for ARV provision will fall short by R1-billion if the numbers of infected people continue to grow at their current pace.

Now Appearing on LA Billboards and Online, Campaign Directs Public to www.freeHIVtest.net for Info on Free, Fast and Convenient HIV Testing Locations; Encourages Personal Responsibility and Need for Individuals to Know HIV Status to Protect Partners

Campaign is Part of AHF's Year-Long Initiative to Test 40,000 People for HIV in Los Angeles

Screening HIV-positive people with smear-negative pulmonary TB for high levels of C-reactive protein can detect the presence of active TB with a fairly high degree of accuracy, suggesting that C-reactive protein could provide the basis for a point of care test to detect active TB in smear-negative cases in high burden settings, according to findings come from a study presented at the Fourth South African AIDS Conference in Durban in early April.

Top four needs of people with HIV in the UK all related to mental health

Anxiety and depression, self-esteem, sleep and sex are the areas of life that pose problems to the greatest number of people living with HIV in the UK, according to a new study published by Sigma Research. They note that these problems relate to the intimate details of personal experience and quality of life, rather than practical and physical problems.

FDA cautions that Kaletra should not be used by patients with heart rhythm problems or underlying heart conditions

Drug regulatory authorities in the United States have updated the product labelling of the protease inhibitor lopinavir/ritonavir Kaletra, warning that it should not be prescribed to individuals with either heart rhythm problem or any underlying heart problems.

In a genetic leap that could help fast track vaccine and drug development to prevent or tame serious global diseases, DMS researchers have discovered how to destroy a key DNA pathway in a wily and widespread human parasite. The feat surmounts a major hurdle for targeting genes in Toxoplasma gondii, an infection model whose close relatives are responsible for diseases that include malaria and severe diarrhea.

Mutations that help HIV hide from the immune system undermine the virus's ability to replicate, show an international team of researchers in the April 13 issue of the Journal of Experimental Medicine. The study was published online on March 23.

The calendar year in which HIV patients initiated HAART and durability of the nucleoside/nucleotide reverse transcriptase (NRTI) backbone are significant predictors of virological success and treatment failure, according to a study published in the April 6, 2009 early online edition of the Journal of Acquired Immune Deficiency Syndromes.

HIV positive individuals taking combination antiretroviral therapy (ART) commonly develop reduced bone mineral density (BMD), a metabolic disorder. This high prevalence of osteopenia and the more severe osteoporosis has been linked to various factors including HIV infection itself, aging of this population, lower body weight, and smoking. Although some studies suggest that reduced BMD is associated with use of protease inhibitors (PIs), others have not confirmed these findings.

In an effort to reduce the risk of sexual transmission of HIV among heterosexuals, researchers have explored a variety of women-controlled methods including vaginal microbicides. Microbicides are gels, films, or other products inserted prior to intercourse. A similar strategy could potentially be used to prevent HIV transmission during anal sex.

On April 7, 2009, the Kaiser Family Foundation and the National Alliance of State and Territorial AIDS Directors (NASTAD) released the "2009 National ADAP Monitoring Project Annual Report," followed the next day by NASTAD's monthly "ADAP Watch" for April.

At the 13th International Symposium on Viral Hepatitis and Liver Disease (ISVHLD), held May 20-24, 2009 in Washington, DC, experts were invited to present their views on various issues related to viral hepatitis. Dr. T.J. Liang of the Liver Diseases Branch of the National Institute of Diabetes and Digestive and Kidney Diseases (part of the National Institutes of Health) offered a summary of his views on the history and prospects for development of a vaccine to prevent hepatitis C virus (HCV) infection. Following are edited excerpts from his remarks.

Over years or decades, chronic hepatitis C virus (HCV) infection can lead to advanced liver disease, including cirrhosis and hepatocellular carcinoma (HCC). Sustained response to interferon-based therapy dramatically reduces the risk of liver disease progression, but does not eliminate it completely, according to 2 recently published studies.

People living with HIV who do not start highly active antiretroviral treatment until their CD4+ T cell counts drop below 200 might not be able to reach a normal CD4 cell count, even after 10 years of otherwise effective treatment, according to a study in the March 15 issue of Clinical Infectious Diseases, Reuters reports. According to Reuters, an HIV-positive person is considered to have a normalized immune status after CD4 counts are maintained above 500.

Although the results of a study comparing early and deferred antiretroviral treatment scheduled to be published in the April 30 issue of the New England Journal of Medicine are "striking," they "cannot be considered definitive evidence that everyone with HIV should start receiving antiretroviral therapy," Paul Sax and Lindsey Baden of the Division of Infectious Diseases at Brigham and Women's Hospital write in an NEJM editorial.

A Chinese woman holds a red ribbon to show solidarity with HIV carriers and AIDS patients during an AIDS campaign in Tianjin, China, in November 2008

Time.com on Wednesday examined China's efforts to curb the spread of HIV/AIDS and address the rising number of related deaths in the country. China announced in February that HIV/AIDS was the country's No. 1 deadly infectious disease in 2008, resulting in almost 7,000 deaths in the first nine months of last year. Time.com reports that the "fact that HIV ... is a significant and increasing cause of death" in the country "shows that government programs are not reaching enough people." Bernhard Schwartlander, coordinator of UNAIDS in China, said that it is "very difficult" to discuss sex in China's schools, workplaces and relationships. He added, "If they don't know about it, how can they protect themselves?"

Bioalliance Pharma To Complete NDA For Loramyc(R) With Data On Debossed Mucoadhesive Tablet

BioAlliance Pharma SA (Paris: BIO), the specialty pharmaceutical company focused on the treatment of opportunistic infections in cancer and AIDS, announced that the FDA did not accept the NDA for Loramyc® (miconazole) mucoadhesive buccal tablet (MBT) to be filed based on the lack of a tablet imprint code. Loramyc® was approved in Europe in 2007 and is currently marketed in several EU territories including France, Germany, the UK, Sweden, Finland and Denmark. While the EU does not require a unique tablet identifier, the U.S. FDA does require a tablet imprint code for drug identification purposes. Prior to the initial filing, BioAlliance initiated the development of a debossed tablet to fulfill this requirement. BioAlliance will work closely with the FDA on the introduction of the debossed tablet and will soon after resubmit the Loramyc® application.

NEUROLOGICAL IMPACT OF HIV: HIV infection in the brain: a long-term limitation of HAART?

The recent focus on the impact of unsuppressed viral replication in the SMART and other studies, has lead to emerging concerns that overlap the issues of aging, cardiovascular health, bone disease and higher rates of some cancers. For the last three years at CROI, neurological function has expanded from the previous single lectures to full plenary sessions. This year provided perhaps the most compelling and concerning results yet from many different research approaches.

Among HIV-infected patients living in Thailand, the single most important determinant of survival during TB treatment was use of ART. Controlled clinical trials are needed to confirm the findings that early ART initiation improves survival and that the choice of non-nucleoside reverse transcriptase inhibitor does not.

Nef alleles from different lineages of SIVsmm do not require adaptive changes to be functionally active in human cells. Strain rather than lineage-specific differences in Nef function may impact the virological and immunological feature of SIVsmm in SMs and possibly affected viral fitness and pathogenicity in human and macaque hosts.

Isolation and characterization of a small antiretroviral molecule affecting HIV-1 capsid morphology

A-hydroxy-glycineamide has an unusually simple structure and a novel mechanism of antiviral action. Thus, a-HGA could be a lead for new antiviral substances belonging to a new class of anti-HIV drugs, i.e. capsid assembly inhibitors.

The authors present a case of primary meningococcal arthritis caused by N meningitidis serogroup X as the initial presentation of a patient with previously undiagnosed HIV. The diagnosis was made based on arthrocentesis results showing Gram-variable cocci and monosodium urate crystals in the synovial fluid.

The results suggest that ITK deficiency causes what we believe to be a novel immunodeficiency syndrome that leads to a fatal inadequate immune response to EBV. Because ITK deficiency resembles EBV-associated lymphoproliferative disorders in boys, the authors suggest that this molecular cause should be considered during diagnosis and treatment

Considering the significantly lower frequency of the high production haplotype and the higher frequency of the low production halplotype of TGF-, low production of this cytokine is expected in some CVID patients.

South Africa: How the Free State ARV Moratorium Breached the Constitution

The government has violated the Constitution by imposing a moratorium on the roll-out of antiretroviral drugs, for new HIV/AIDS patients in the Free State, the AIDS Law Project recently told a civil society gathering in Bloemfontein.

Darmstadt, Germany - A member of Germany's leading female pop band has been arrested for allegedly having unprotected sex despite being HIV positive, lawyers said Tuesday. Nadja Benaissa, a 26-year-old singer with the group No Angels, is to have had unprotected sex with three men in 2004 and 2006, the state prosecution in the town of Darmstadt said.

One of the three men is now HIV positive, possibly as a consequence of his sexual relations with Benaissa.

“Gynaecomastia [breast enlargment] is a frequent side effect of antiretroviral therapy (ART) and is seen earlier and more frequently in our patient population than in European cohorts,” said Dr Tom Heller, the HIV and TB Coordinator in the Hlabisa district in the Northern KwaZulu-Natal at the South African AIDS Conference earlier this month.

Over a third of gay men infected with strain of HPV most associated with anal cancer

Anal infection with human papilloma virus (HPV) is at near universal levels in gay men, a study conducted in Australia and published in the online edition of Sexually Transmitted Infections has found. Significant numbers of men were infected with strains of the virus that carry a high risk of cancerous and pre-cancerous cell changes in the anus.

The process of HIV entry begins with the binding of the viral envelope glycoprotein gp120 to both the CD4 receptor and one of CXCR4 or CCR5 chemokine coreceptors. There is currently considerable interest in developing novel ligands which can attach to these coreceptors and hence block virus-cell fusion. This article compares the application of structure-based (docking) and ligand-based (QSAR analyses, pharmacophore modeling, and shape matching) virtual screening tools to find new potential HIV entry inhibitors for the CXCR4 receptor. The comparison is based on retrospective virtual screening of a library containing different known CXCR4 inhibitors from the literature, a smaller set of active CXCR4 inhibitors selected from a large combinatorial virtual library and synthesized by us, and some druglike presumed inactive molecules as the reference set.

The US Food and Drug Administration (FDA) approved changes on April 6 to the product label for lopinavir/ritonavir tablets and oral solution (Kaletra, Abbott Pharmaceuticals) and also issued a new medication guide. The new labeling changes include warnings and precautions regarding QT/QTC interval and PR interval prolongation.

Three recent African trials support male circumcision for reducing the risk of contracting HIV in heterosexual men. After including new data from these trials in their review, Cochrane Researchers have changed their previous conclusions that there was insufficient evidence to recommend circumcision as an intervention to prevent HIV infection in heterosexual men.

The AIDS-causing HIV specifically counteracts the mechanisms of human cells that protect these against viral infections – a special viral protein marks protective cellular proteins for their rapid destruction and thus diminishes the cell's supply. A team of researchers in Heidelberg under supervision of virologist Dr. Oliver Keppler demonstrated this mechanism for the first time in cell cultures, thus discovering a target for a novel treatment strategy. Another important discovery of the Heidelberg virologists – this strategy of the human HIV is not effective in a rat model for AIDS. The protective protein in rats is immune to HIV counteraction. Consequently, HIV cannot propagate itself as easily in the animal model as in humans – one limitation of the current rat model. However, this new knowledge may enable an improvement of the small animal model developed by the Heidelberg researchers. The study was published in the journal Cell Host & Microbe in March 2009.

Etravirine is the first next-generation nonnucleoside reverse-transcriptase inhibitor (NNRTI) that is approved for the treatment of HIV infection in patients who have experienced virologic failure while receiving an NNRTI-containing regimen. Etravirine demonstrates potent in vitro activity against wild-type and NNRTI-resistant strains of HIV. The major adverse effects of etravirine therapy are nausea and rash, which are typically self-limiting and do not lead to treatment discontinuation.

The RNA extraction method is an important factor in obtaining reliable RNA quantification and PCR amplification of HIV-1 on DPS/DBS. DBS could be used as an alternative for DPS depending on HIV RNA cutoffs for virological failure. VL measurements remain stable over a longer period than do PCR amplification results

In the clinical setting, PET has been shown to allow the differentiation of AIDS-related opportunistic infections and malignancies, and to allow monitoring of side effects of HAART. However,in patients suffering from HIV infection and presenting with extracerebral lymphoma or other human malignancies, knowledge of viraemia is essential when interpreting FDG PET imaging.

Mathematical Analysis of a Two Strain HIV/AIDS Model with Antiretroviral Treatment

A two strain HIV/AIDS model with treatment which allows AIDS patients with sensitive HIV-strain to undergo amelioration is presented as a system of non-linear ordinary differential equations. The disease-free equilibrium is shown to be globally asymptotically stable when the associated epidemic threshold known as the basic reproduction number for the model is less than unity. The centre manifold theory is used to show that the sensitive HIV-strain only and resistant HIV-strain only endemic equilibria are locally asymptotically stable when the associated reproduction numbers are greater than unity. Qualitative analysis of the model including positivity, boundedness and persistence of solutions are presented. The model is numerically analysed to assess the effects of treatment with amelioration on the dynamics of a two strain HIV/AIDS model. Numerical simulations of the model show that the two strains co-exist whenever the reproduction numbers exceed unity. Further, treatment with amelioration may result in an increase in the total number of infective individuals (asymptomatic) but results in a decrease in the number of AIDS patients. Further, analysis of the reproduction numbers show that antiretroviral resistance increases with increase in antiretroviral use.

BBC News on Sunday examined how the Bwindi Community Hospital -- located in a remote region on the border between Uganda and the Democratic Republic of Congo -- has improved its capacity to monitor HIV-positive people using a portable blood-testing device, called the PointCare NOW machine. According to BBC News, the Bwindi hospital provides health care to about 40,000 people, including 1,000 people living with HIV.

"When it comes to fighting the HIV/AIDS epidemic in the United States, there is an alarming complacency among Americans," a Washington Post editorial says. It adds, "Perhaps it's the success of antiretroviral drug treatments. In the eyes of many, those drugs have transformed the disease from one with no cure to a manageable ailment." It might be the "view that AIDS is more of a worry in Africa or Southeast Asia," the editorial says, adding, "But it's not just happening 'over there.' And the Obama administration took a first step last week to remind people that it's happening right here, right now."

Cornelius is currently performing a pilot study to test the effectiveness of text messaging as a medium for delivering HIV prevention education to at-risk teens. The study is first of its kind to be performed and is being funded by the National Institutes of Health's National Institute of Nursing Research.

Proposed Informed Consent Requirement for Routine HIV Tests in New York Could Affect Minorities' Access to Treatment, Advocates Say

Some minority advocacy groups are opposing proposed legislation in New York state on HIV testing consent requirements, saying they could pose a barrier for minorities, who are disproportionately affected by HIV/AIDS, the Rochester Democrat and Chronicle reports. The groups say that the bill falls short of addressing the HIV/AIDS crisis, particularly among the minority community, because it does not remove the permission requirement altogether.

UCL Wins Four Grants from EPSRC to Support Research into Nanotechnology for Healthcare Purposes

UCL has won four grants worth a total of just over £5million from the Engineering and Physical Sciences Research Council (EPSRC) to support research into large-scale integrated projects that exploit nanotechnology for healthcare purposes.

The projects will focus on using nanotechnologies –systems that function at the level of molecules – to advance knowledge and treatment of cancer, dementia and HIV.

The projects funded through the council’s ‘Nanoscience through Engineering to Application’ programme, which supports research that aims to develop nanotechnologies for the targeted delivery of therapeutic agents and for healthcare diagnostics.

Genetic Immunity is pleased to announce the commencement of an exploratory Phase II clinical trial of the Company's DermaVir Patch HIV nanomedicine vaccine lead product candidate being conducted at Policlinico San Matteo in Pavia, Italy.

This Phase II, randomized, placebo-controlled trial is designed to investigate whether therapeutic immunization during highly active antiretroviral therapy (HAART) induces elevations of HIV-specific memory T cells in HIV-1-infected individuals, and whether the quantity of these memory T cells correlate with the viral load set point following analytical treatment interruption (ATI). Subjects are being randomized to receive either DermaVir Patch (8 subjects per cohort) or Placebo Patch (8 subjects per cohort) every four weeks for three applications while receiving maximally suppressive HAART. HAART will be discontinued at Week 9 for an ATI period of 20 weeks. The trial will employ a novel assay of memory T-cell function known as the PHPC (Precursors with High Proliferative Capacity) assay developed by ViroStatics, srl, the Italian partner of Genetic Immunity.

Illicit drug injectors are at serious risk of catching the lethal illness tuberculosis (TB), with 67 per cent of users testing positive for the infection in a recent study.

According to new research, more than two thirds of injection drug users in Tijuana, Mexico, tested positive for TB, highlighting an urgent need for screening for the contagious infection among this at-risk demographic.

Today, GlaxoSmithKline and Pfizer announced a deal that’s a larger-scale version of the third type: They’re combining their HIV businesses, forming a separate HIV company that could be valued at as much as $7.5 billion based on expected sales.

The deal is meant to help both companies mitigate some of their problems. Glaxo is a big seller of HIV drugs, including Combivir and Epzicom, but its products are relatively old and aren’t growing so briskly, while its pipeline of HIV drugs in development is relatively week, the WSJ says. Meanwhile, Pfizer has a bunch of HIV drugs in development but doesn’t have as many products now being sold. (Selzentry is its young HIV drug on the market.)

New AIDS Research Training Grants Awarded For Projects In 15 Countries: Funds Support U.S. Universities in Collaboration With Low-and Middle-Income Countries

The Fogarty International Center of the National Institutes of Health has awarded seven grants totaling almost $2.7 million to train HIV/AIDS researchers in 15 low- and middle-income countries.

The funds are awarded under the center's 20-year-old signature AIDS International Training and Research Program, which has trained nearly 2,000 foreign researchers, most of whom remain in their countries to battle the epidemic, train young scientists and move into government health leadership.

Canada Should Pass Bill That Would Expedite Export Of Low-Cost Drugs For HIV, Other Diseases, Opinion Piece Says

"For many years, countries such as Canada have avoided the uncomfortable truth that millions are dying in the developing world due partly to legal barriers that render access to medicines unaffordable," Michael Geist, chair of Internet and E-commerce law at the University of Ottawa, writes in a Toronto Star opinion piece in response to a recently introduced bill that would reform Canada's Access to Medicines Regime by expediting the process of exporting generic drugs for diseases such as HIV to developing countries.

Starting Antiretroviral Treatment Earlier Could Reduce The Risk Of Death By Up To 94 Percent

Begin treatment as early as possible: this general common sense rule seems to apply to most diseases except HIV-AIDS, which is only treated once a certain number of immune cells called "CD4+" cells have disappeared. The results of a North American study, which involved the team of Dr. Marina Klein of the Research Institute of the MUHC, run contrary to this consensus. The findings show that the risk of death in seropositive patients decreases by 69% to 94% if they start treatment earlier than officially recommended.

Highly restricted T-cell receptor repertoire in the CD8+ T-cell response against an HIV-1 epitope with a stereotypic amino acid substitution

The results provide an example of restricted TCR repertoire in a specific CTL response against the escaping epitope. The authors speculate that impairment of antigen presentation in escaping viruses may underlie the restricted repertoire.

Although rs9264942 and B*57 (but not rs2395029G) are clearly associated with control of viral load set-point among African-Americans, fine-mapping of MHC SNPs in populations of African and European descent should help reveal the causative variants and the underlying functional mechanisms.

Morphologic and metabolic abnormalities in vertically HIV-infected children and youth

In a large group of vertically HIV-infected children and youth with extensive antiretroviral therapy exposure, height, weight, and total and limb fat were lower than in controls. There was a high prevalence of lipid abnormalities among those on protease inhibitors and evidence of developing insulin resistance, factors that may accelerate lifetime risk for cardiovascular disease.

The prevention of tuberculosis, diarrhoea, and, in endemic regions, malaria; the addressing of debilitating depression; cervical screening; and the management of chronic cardiovascular disease and its risk factors are all of benefit to patients accessing HIV/AIDS care. As family-centred care models develop in resource-limited settings, the availability of evidence-based service packages such as presented here will help program designers prioritize available human and materiel resources toward those interventions that improve patients' global health and well being.

The major obstacle to development of a vaccine has been the absence of naturally acquired protective immunity, which is characteristic of most infectious agents. The authors and others, however, have identified individuals who appear to be resistant to infection. Using a combination of epidemiology, molecular biology, and genetics, the authors hypothesize that these individuals are able to resist infection by clearing low doses of HIV from their systems. The authors further hypothesize that they are able to clear the virus through a highly efficient system of processing and presentation of HIV epitopes (antigens) to CD8+ cytotoxic cells, which activate them to remove virally infected cells. Subsequent studies have lent support to this hypothesis.

The authors also observed a high risk of low antibody levels in response to the DTwP vaccine in HIV-infected children with severe immunodeficiency. The concentrations of antibodies induced by the DTwP vaccine were lower in HIV-infected children than in uninfected children. This study supports the need for a booster dose of the DTwP vaccine in order to maintain high antibody levels in HIV-infected children.

An increasing population of aging HIV-positive patients with a spectrum of antiretroviral therapies and accumulation of endocrine abnormalities and conventional cardiovascular risk factors will present preventive and therapeutic challenges to the health-care system.

Gilead Sciences today announced that it has begun enrolling patients in a Phase II clinical trial of its investigational integrase-based, single-tablet, once-daily regimen of elvitegravir, GS 9350 and Truvada® (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) for the treatment of HIV-1 infection. GS 9350 is an investigational compound being developed as a pharmacoenhancing or “boosting” agent to increase blood levels and allow once-daily dosing for certain medicines, including Gilead’s investigational HIV integrase inhibitor, elvitegravir. The Phase II study is designed to evaluate the safety and efficacy of the regimen compared to once-daily Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg). The study will enroll 75 HIV-1 infected, antiretroviral treatment-naïve adults across approximately 50 investigative sites in the United States.

MBABANE, 15 April 2009 (IRIN) - Anecdotal evidence that entrenched cultural beliefs among Swazis actively encourage the spread of HIV/AIDS has been confirmed by a joint government and UN report.

The study by UN the Population Fund (UNFPA) and Swaziland's Ministry of Health and Social Welfare - The State of the Swaziland Population - echoes warnings by local NGOs that "AIDS cannot be stopped unless there is a change in people's sexual behaviour."

Despite consistent efforts to curtail the most severe AIDS epidemic in the world, it appears to have gained ground. "Swazis are very traditional people, and their sexual behaviour is inbred and totally against safe sexual practices, like condom use and monogamous relationships, that limit the spread of HIV," Thandi Mngomezulu, an HIV testing counsellor in Manzini, the country's main commercial city, told IRIN.

A standard dose of efavirenz significantly lowered darunavir concentrations when healthy volunteers added the nonnucleoside to 900/100 mg of darunavir/ritonavir once daily [1]. Because darunavir's minimum concentration never fell below the 50% effective concentration (EC50) of darunavir for nonresistant virus (55 ng/mL), investigators from the National University of Singapore and Johns Hopkins University in Baltimore suggested this may be a viable regimen for previously untreated people without resistant virus. But they cautioned that their results need to be confirmed in people with HIV.

Darunavir/ritonavir taken once daily at a dose of 900/100 mg worked well in a nonrandomized study of 25 people with some antiretroviral experience, including one or more previous protease inhibitors (PIs) [1]. No one in this study had darunavir-related mutations before starting darunavir/ritonavir. Once-daily 800/100-mg darunavir/ritonavir is licensed for treatment-naive patients, but the sanctioned dose for experienced people remains 600/100 mg twice daily. The study by Barcelona clinicians involved 25 people, 12 of them with a viral load under 50 copies. Among people with a detectable load, the median load was 20,000 copies/mL. Median CD4 count stood at 330 and median body mass index at 24 kg/m(2). Thirteen people had HCV infection. The study group had a median of 2 nucleoside-related mutations and 2 nonnucleoside mutations, but a median of 0 PI mutations (range 0-2) meaning some people had a few PI mutations. No one had a darunavir-specific mutation. People had taken a median of 5 earlier regimens, including 2 PI regimens, and a median of 1 PI regimen had failed. All study participants began 900/100 mg of darunavir/ritonavir once daily with at least one other drug judged to be active against their virus. (Four people took raltegravir.) After 6 months, everyone had an undetectable viral load and the median CD4 count rose by 67. Liver function and lipid profiles did not change significantly. No one had a serious side effect, and no one stopped treatment.

10th Int PK Wrkshp: How Much (or How Little) Ritonavir Do You Need to Boost Another PI?

Protease inhibitors (PIs) fall into two groups--those whose concentration correlates closely with the boosting dose of ritonavir, and those that do not--according to a 16-study systematic analysis by Andrew Hill (University of Liverpool) and colleagues at other centers [1]. Finding the lowest effective boosting dose could cut costs and lower the risk of side effects. Hill suggested 50 mg of ritonavir once daily--or less--may be enough to boost some PIs.

Several trials have scrutinized lopinavir/ritonavir monotherapy as a simple maintenance or first-line antiretroviral regimen [1]. Now British clinicians and pharmacologists proffer a different reason for giving lopinavir/ritonavir with no other antiretrovirals--as a way to take people off their antiretroviral regimen without running the risk of resistance [2]. Steve Taylor (Birmingham Heartlands Hospital) and colleagues at other centers call it "a universal ART stopping strategy."

10th Int PK Wrkshp: Genetic Markers Tied to Early Discontinuation of Three Antiretrovirals

Pharmacogenetic markers that purportedly signal antiretroviral side effects predicted discontinuation of atazanavir, efavirenz, and tenofovir (but paradoxically not abacavir) within the first year of treatment in the Swiss HIV Cohort Study (SHCS) [1]. Sara Colombo and colleagues cautioned that gender and ethnicity also correlated with stopping antiretrovirals and complicate interpretation of their results. But they plan a randomized study to see if monitoring patients for toxicity-related genetic shifts can improve antiretroviral care.

In the absence of a vaccine, three bold new approaches to controlling the HIV/AIDS pandemic are being discussed by those working in medicine and public health. These approaches are still in the conceptual and testing phases, but if applied as a group, it's possible they could have a dramatic effect.

The first complete update in five years of the U.S. guidelines for preventing and treating HIV-associated opportunistic infections has been released by the National Institutes of Health and the Centers for Disease Control and Prevention in cooperation with the HIV Medicine Association of the Infectious Diseases Society of America (IDSA).

The new Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents apply state-of-the-art science and medicine to 29 infectious diseases of concern. More than 140 medical experts contributed their knowledge to this edition of the guidelines, released on April 10.

The AIDS-causing HIV specifically counteracts the mechanisms of human cells that protect these against viral infections - a special viral protein marks protective cellular proteins for their rapid destruction and thus diminishes the cell's supply. A team of researchers in Heidelberg under supervision of virologist Dr. Oliver Keppler demonstrated this mechanism for the first time in cell cultures, thus discovering a target for a novel treatment strategy.

Bone loss during HIV treatment most associated with protease inhibitors

Over a third of HIV-positive patients about to start antiretroviral treatment have reduced bone mineral density, French investigators report in the April 27th edition of AIDS. The researchers also found that bone mineral density continued to fall after starting HIV treatment, particularly in individuals who were taking a protease inhibitor. People with HIV are more likely to have conditions such as osteopenia (low bone mineral density) and osteoporosis (weakened bones) than HIV-negative individuals of the same age and sex. Factors such as low body weight and increased levels of smoking may contribute to this. It is also thought that HIV infection itself may be a cause. Some studies have also found an association between the use of HIV treatment and a loss of bone mineral density. The results of this research are conflicting, but some have shown that treatment with protease inhibitors or tenofovir lead to a loss of bone.

A new book, the Virus, Vitamins and Vegetables, documenting the South African government's controversial response to the AIDS epidemic was launched in Durban and Johannesburg, recently.

The Virus, Vitamins and Vegetables is a compilation of essays by journalists, activists, doctors and scientists. Each of the 13 writers tells of what they have witnessed of the government's response or lack, thereof, to the AIDS epidemic under Thabo Mbeki and Manto Tshabalala-Msimang, both fallen from their positions as president and Health Minister, respectively. The book is set against the backdrop of a period in the 1990s when Mbeki questioned the causal link between HIV and AIDS and his Health Minister promoted beetroot and garlic and other alternatives over antiretrovirals as treatment for AIDS.

Some People Do Not Achieve Complete CD4 Cell Recovery even after 10 Years on Suppressive Antiretroviral Therapy

People who take combination antiretroviral therapy (ART) typically experience an increase in their CD4 count as their viral load falls, but this is not always the case. Despite suppressive treatment, some patients who started therapy with a low CD4 count may not achieve full immunological recovery even after 10 years, according to a study published in the March 15, 2009 issue of Clinical Infectious Diseases.

Suboptimal Adherence May Have Less Detrimental Effect in Patients Taking Boosted Darunavir (Prezista)

Several studies in the era of highly active antiretroviral therapy (ART) have indicated that near-perfect adherence is important for achieving optimal outcomes. But some drugs are more "forgiving" of suboptimal adherence than others.

Research has shown that treatment failure is more likely to occur when patients do not achieve complete adherence to non-nucleoside reverse transcriptase inhibitors (NNRTIs) compared with ritonavir-boosted protease inhibitors. Now, a study presented at the 15th British HIV Association Meeting (BHIVA 2009) this month in Liverpool suggests there are also differences among drugs in the protease inhibitor class.

CCR5 antagonists, a type of HIV entry inhibitor, represent one of the newest classes of antiretroviral therapies. The first CCR5 antagonist, maraviroc (Selzentry), was approved in August 2007, shortly before the first integrase inhibitor, raltegravir (Isentress).

Last week Tobira Therapeutics announced that it has started a randomized Phase 2a proof-of-concept study of a new CCR5 antagonist candidate, TAK-652, to be conducted in the U.S. and Argentina.

Bone loss (osteopenia or the more severe osteoporosis) is common in people with HIV, although it remains unclear whether this is due to HIV infection itself, antiretroviral drugs such as tenofovir (Viread, also in the Truvada and Atripla combination pills), the normal aging process as HIV positive people survive longer, or some combination of factors.

Decreased bone mineral density (BMD) occurs when the activity of osteoblasts (cells that build new bone tissue) and osteoclasts (cells that re-absorb bone) gets out of balance, but the mechanisms underlying this imbalance in HIV positive people is not fully understood.

In 1976, the noted human geneticist James Neel titled a book chapter "Diabetes Mellitus: A Geneticist's Nightmare."1 Over the past 30 years, however, the phenotypic and genetic heterogeneity of diabetes has been painstakingly teased apart to reveal a family of disorders that are all characterized by the disruption of glucose homeostasis but that have fundamentally different causes. Recently, the availability of detailed information on the structure and variation of the human genome and of new high-throughput techniques for exploiting these data has geneticists dreaming of unraveling the genetic complexity that underlies these disorders. This review focuses on type 1 diabetes

Effect of pulmonary tuberculosis on mortality in patients receiving HAART

The increase in death that the authors observed among individuals with PTB at the time of HAART initiation appears not to be due to the to the presence of PTB, but instead to confounding factors such as low CD4 cell count, low BMI, and WHO stage IV disease. These results further demonstrate that initiation of HAART soon after initiation of PTB treatment is not likely to put patients at higher risk of death.

Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir

Exposure to TDF is associated with an increased risk over time of kidney tubular abnormalities in the absence of significant impaired glomerular function. Although long-term consequences of this tubulopathy are unknown, close monitoring of accelerated bone mineral loss and renal insufficiency are warranted. Periodic screening of tubular function parameters should be recommended to patients receiving TDF.

NFV and M8 exhibited partial drug transfer and/or accumulation in the amniotic compartment, whereas ZDV and 3TC concentrations mostly exceeded that in maternal plasma. Overall, all drugs achieved exposures in the amniotic fluid in excess of their wild-type viral susceptibilities. Amniotic fluid is an important compartment in the prevention of mother-to-child transmission.

Effects of First-Line Use of Nucleoside Analogues, Efavirenz, and Ritonavir-Boosted Protease Inhibitors on Lipid Levels

The PIs showed two different types of lipid elevations: Group 1: saquinavir/r, atazanavir/r, and darunavir/r; and Group 2: lopinavir/ritonavir and fosamprenavir/r. There were greater elevations in total cholesterol and triglycerides for Group 2 compared to Group 1 but no differences in LDL or HDL between Group 1 and Group 2. Patients treated with efavirenz showed similar rises in total cholesterol and LDL compared with the PIs in Group 2 but showed smaller rises than in Group 1. There is a wide range of lipid elevations during 48 weeks of first-line HAART, which depends on the choice of antiretrovirals used.

Unprotected sex following HIV testing among women in Uganda and Zimbabwe: short- and long-term comparisons with pre-test behaviour

HIV-infected women reduced the number, but not the proportion, of unprotected acts. HIV-negative women did not increase condom use after testing and counselling, but neither did they decrease condom use, suggesting that testing negative was not interpreted as endorsement of risky behaviour.

Caution, prudence, assumption of infection, and proven clinical methodologies comprise the best course of action for the hearing health care professional. This enables audiologists to deliver required medical and quality of life services in a manner that is safe for the practitioner, staff, and patients.

Transmission risk is greatest when mother and offspring both have low CCL3L or CCL4L gene doses. The impact on HIV-AIDS susceptibility of the chemokine gene-rich locus on 17q12 is dependent on the balance between the doses of genes conferring protective (CCL3La and CCL4La) versus detrimental (CCL4Lb) effects. Hence, the combinatorial genomic content of distinct genes within a copy number variable region may determine disease susceptibility.

Darunavir minimum concentration (Cmin) was 45% lower with once-daily dosing (for antiretroviral-naive people) than with twice-daily dosing (for experienced patients), according to an observational study of 138 patients who started darunavir/ritonavir at three French hospitals. But Cmin exceeded target concentrations for almost everyone in this study. Raltegravir or nonnucleosides had little impact on darunavir Cmins in this population

Etravirine trough concentrations were significantly higher when patients already taking darunavir/ritonavir added etravirine than when they started the drugs together. Whether this difference will hold true for most people starting these two antiretrovirals sequentially is difficult to say because of the small size of this comparison.

Replacing enfuvirtide with raltegravir in a salvage regimen lowered concentrations of the protease inhibitors (PIs) darunavir and tipranavir in the French EASIER trial. However, minimum and maximum concentrations (Cmin and Cmax) of the PIs stayed in the range of previously reported levels, reported Anne-Marie Taburet, and the falling PI concentrations in EASIER had no apparent impact on virologic outcome.

Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial

Zoledronic acid was non-inferior and superior to risedronate for increase of lumbar spine bone mineral density in both the treatment (least-squares mean 4·06% [SE 0·28] vs 2·71% [SE 0·28], mean difference 1·36% [95% CI 0·67-2·05], p=0·0001) and prevention (2·60% [0·45] vs 0·64% [0·46], 1·96% [1·04-2·88], p<0·0001) subgroups at 12 months. Adverse events were more frequent in patients given zoledronic acid than in those on risedronate, largely as a result of transient symptoms during the first 3 days after infusion. Serious adverse events were worsening rheumatoid arthritis for the treatment subgroup and pyrexia for the prevention subgroup.

Glucocorticoids are used to treat many disorders. Their negative effect on skeletal health is a substantial drawback, such that their use is the most frequent secondary cause of osteoporosis.1 30-50% of patients who take glucocorticoids chronically have a fracture. Glucocorticoids decrease bone formation by reducing the lifespan of osteoblasts and osteocytes (figure).

HIV-1 Infection Is Associated With an Earlier Occurrence of a Phenotype Related to Frailty: HIV+ men in MACS 10-Times More Likely to Exhibit Frailty than HIV-negative Men.

In this study, both HIV infection and AIDS were predictors of frailty-like manifestations, and the duration of HIV infection was associated with the likelihood of these manifestations. The observed increases of FRP with low CD4 T-cell count and high HIV viral load, two biomarkers of HIV disease progression, suggest a common underlying biology between frailty and HIV disease. However, the presence of the FRP was far from automatic in men with HIV or AIDS. Finally, in this study, HIV infection for ?4 years appeared to confer a rate of FRP comparable to that of HIV-uninfected men 10 years older, and this rate was further increased by 2- to 3-fold for men infected > 4 years and an additional 2-fold for men with AIDS.

It has been posited that HIV infection demonstrates similarities to aging and possibly to frailty (54). Specifically, HIV infection is associated with diverse impairments that resemble frailty, such as myopathy, loss of muscle mass and weight, fatigue, functional impairments, cognitive dysfunctions and motor abnormalities, as well as rheumatological disorders and neuropathies, even in the absence of identifiable opportunistic illnesses.

This study extends a previous report in which we defined a FRP (frailty-related phenotype)38 to approximate the clinical definition of a frailty phenotype by Fried et al16 and showed it to be associated with HIV-1 infection.A low CD4 T-cell count was an independent significant predictor of the FRP in HIV-positive men, adjusting for AIDS, and also in the absence of having a wasting syndrome. Furthermore, the association between CD4 T-cell count and the FRP remained the same after restriction to HAART-treated men with a good virological response to HAART (whether they had a CD4 cell response or not) or after taking into account hepatitis B or C status and depressive symptoms. These findings provide evidence that the FRP is etiologically related to a compromised immune system as associated with HIV infection. Of note, the findings of the present study parallel other work in older HIV-uninfected individuals which indicates that a compromised immune system is associated with frailty and predictive of mortality.27,56-58 Taken together, these findings support the notion of a common etiology of frailty associated with aging and with HIV.Of note, we estimated that in the current HAART era, the impact of a 10-year increase in age was similar to that of a decrease of 250 CD4 T cells per cubic millimeter for average ages and CD4 T-cell counts

This study shows that effectiveness of sdNVP may be compromised by prior exposure to sdNVP, although the increase in transmission rate after prior exposure could not be explained by the detection of NVP resistance mutations prior to re-exposure as measured both by standard genotyping and highly sensitive allele-specific PCR assays. Furthermore, transmission rates of women with prior exposure were not higher than those reported elsewhere.

Current PrEP trials are using oral tenofovir (Viread), oral co-formulated emtricitabine-tenofovir (Truvada), or intravaginal tenofovir gel, the last an indication of the direction that the topical microbicide field has taken into incorporating antiretroviral agents into its products. The scale of the current trials is large, with >20,000 participants anticipated to enroll across the eight trials; however, each trial is distinct in its study population and route of HIV exposure, including men who have sex with men, injection drug users, high- and low-risk women, and HIV serodiscordant couples.

In conclusion, this multicentre, open-label study of PLA treatment is the first to demonstrate objectively assessed clinically modest increases in facial volume and soft tissue thickness that were sustained over 48 weeks in injection planes but not in other facial areas. Patient-perceived benefits included aesthetic improvement and enhanced social functioning and QoL; however, psychological benefits were greater in those treated at baseline. The cost of soft tissue augmentation is substantial as third-party providers contribute minimally. It is encouraging to know that treatment delays, necessitated on financial grounds, would not be expected to impact outcomes adversely. The optimal treatment approach for HIV facial lipoatrophy is currently unknown. Research to define and compare the most efficacious filling agents for this distressing condition will require use of validated diagnostic criteria and/or tools to assess lipoatrophy severity and validated measures of facial soft tissue thickness or volume.

The United States must do more to curb the spread of diseases like AIDS and hepatitis C in prison, where infection rates are high and inmates can easily spread disease through unprotected sex or by sharing needles.Drug treatment in prison is clearly part of the solution. But by some estimates, fewer than one in five inmates who need formal treatment are actually getting it. That's alarming, given that about half the prison population suffers from drug abuse or dependency problems.Addicted prisoners cause problems outside the walls. After they're freed, addicts with H.I.V. or AIDS can infect spouses and lovers. They feed their addictions by returning to crime, which lands them back in prison and starts the terrible cycle over again.

Among older patients with type 2 diabetes, a history of severe hypoglycemic episodes was associated with a greater risk of dementia. Whether minor hypoglycemic episodes increase risk of dementia is unknown.

Bristol-Myers Squibb is launching a co-pay assistance program in April for eligible new and existing REYATAZ (atazanavir) and SUSTIVA (efavirenz) patients who are commercially insured and have high co-pays or co-insurance. We recognize that especially in this economic environment, out-of-pocket costs for HIV medicines may be prohibitive even for patients who have prescription drug benefits. This program reflects Bristol-Myers Squibb's ongoing commitment to helping patients who need our medicines to access them.

Treatment Interruption Revisited with LOTTI Study: authors reported interruptions were not inferior to continuous HAART in this study

The LOTTI Study published in April 2009 AIDS finds CD4-guided treatment interruptions within certain parameters to be equal in clinical outcomes to continuous HAART. Patients had to have >700 CD4s and no history of nadir CD4 <200. They restarted HAART if CD4 was <350 and had to remain on HAART until CD4 increased to >700 again. Besides the SMART trial, LOTTI is the largest controlled trial ever performed on CD4 cell-guided STIs.

Etravirine-raltegravir, a marked interaction in HIV-1-infected patients: about four cases

Recently, new compounds, capable of overcoming the extensive class resistances observed in multitreated patients, became available for HIV-infected patients. Raltegravir (RAL) is the first compound of a new class of antiretrovirals, the integrase inhibitors. Etravirine (ETV), a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), has been demonstrated to be active against HIV strains presenting resistance to first-generation NNRTI.

UNITAID and the Clinton Foundation HIV/AIDS Initiative on Friday announced a bulk purchasing agreement with a group of generic drug manufacturers that will reduce the price of some antiretroviral drugs in developing countries, Reuters reports. The discounted prices have been reached for 41 adult and pediatric medications at an average discount of 16% compared with 2008, according to Reuters

President Obama's administration in its fiscal year 2010 budget proposal could flat-line global HIV/AIDS funding at its current level of $5.3 billion, some congressional aides and lobbyists said recently, the Lancet reports. According to the Lancet, the possible funding freeze for global health programs such as the President's Emergency Plan for AIDS Relief might indicate that Obama's "stated goal of expanding prevention and treatment of infectious diseases in poor countries could be on hold" because of the current economic downturn.

Doctors treating open fractures in patients infected with HIV do not need to be more cautious about opportunistic infections compared with HIV-negative patients. The finding, presented by James Aird of Ngwelezane Hospital at the Fourth South African AIDS conference in Durban this month, follows research conducted in KwaZulu-Natal, South Africa.

Estimates of HIV incidence may be unreliable: techniques need refinement

The BED method for estimating HIV incidence should be standardised so that it can be reliably used in an African setting, and the technique needs to be improved to avoid counting people with longstanding HIV infection as recent infections, according to two South African research groups. Their findings were presented at the South African AIDS Conference in Durban earlier this month.

Maternal HIV-positive status shown to be linked to poor vaccination coverage in children

Children born to HIV-positive mothers were 25 to 40% less likely to be vaccinated for childhood diseases, according to findings from a study based on data from rural KwaZulu-Natal, presented at the Fourth South African AIDS Conference in Durban in early April.

Thomas O’Brien, MD, said antibiotic resistance may become a more significant problem in the future because the rate of discovery of new antibiotics has slowed down.

In recent years, prominent infectious disease specialists and leaders of major medical associations have been warning both health care professionals and the general public about the looming potential perils associated with antibiotic resistance.

Patients at South Dakota urology clinic may have been exposed to HIV, hepatitis

Patients treated at a South Dakota urology clinic may have been accidently exposed to HIV and hepatitis after employees of the clinic reused some medical products that were intended to be single-use only.

CHATTANOOGA, Tenn. - Three patients exposed to contaminated medical equipment at Veterans Affairs hospitals have tested positive for HIV, the agency said Friday.Initial tests show one patient each from VA medical facilities in Murfreesboro, Tenn.; Augusta, Ga.; and Miami has the virus that causes AIDS, according to a VA statement.The three cases included one positive HIV test reported earlier this month, but the VA didn't identify the facility involved at the time.The patients are among more than 10,000 getting tested because they were treated with endoscopic equipment that wasn't properly sterilized and exposed them to other people's body fluids.Vietnam veteran Samuel Mendes, 60, said he was surprised to learn of an HIV case linked to the Miami facility, where he had a colonoscopy. He was told he wasn't among those at risk."I was hoping and expecting to not get anyone contaminated like that," he said. "It's probably a little worse than we thought."

Shortage of HIV/AIDS, TB, Malaria Drugs in Ugandan District Could Lead to Treatment Interruption, Drug Resistance

A shortage of HIV/AIDS, tuberculosis and malaria medications in Uganda's northern Gulu district could cause patients to interrupt treatment and lead to drug resistance, Paul Onek, Gulu director of health services, said recently, IRIN/PlusNews reports. According to IRIN/PlusNews, inadequate management of the country's drug supply regularly causes shortages.

The "humanized mouse" developed by Dr. J. Victor Garcia-Martinez has allowed the University of Texas Southwestern physician-scientist to conduct HIV/AIDS studies that would have been impossible without such a small animal model of HIV infection. The virus only infects humans and chimpanzees, which are protected as endangered species. But because the new mouse model is a chimera, with a human immune system, it can be infected. Last year, using these humanized mice, a team of scientists led by Dr. Garcia-Martinez demonstrated that antiretroviral drugs given before and after exposure to HIV could prevent vaginal transmission of the virus. That suggests the possibility that women at high risk of HIV infection might one day be able to take a pill on a regular basis. And, since the drugs tested are already available, having gone through the long and complex approval process, that day might be sooner rather than later.

People living with HIV still refused entry to USA, warns Terrence Higgins Trust

HIV and sexual health charity Terrence Higgins Trust (THT) is warning that people living with HIV remain banned from travelling to the USA unless they have specifically applied for a visa to do so. Despite the recent introduction of an online visa waiver system (ESTA), people living with HIV still need to attend an interview at the American Embassy in London before they can travel legally.

A protein exhibiting an N-terminal amino acid sequence with some similarity to imidazoleglycerol phosphate synthase was purified from fresh Capparis spinosa melon seeds. The purification protocol entailed anion exchange chromatography on DEAE-cellulose, cation exchange chromatography on SP-Sepharose, and finally gel filtration by fast protein liquid chromatography on Superdex 75. The protein was adsorbed using 20mM Tris–HCl buffer (pH 7.4) and desorbed using 1M NaCl in the starting buffer from the DEAE-cellulose column and SP-Sepharose column. The protein demonstrated a molecular mass of 38kDa in gel filtration and sodium dodecyl sulfate–polyacrylamide gel electrophoresis, indicating that it was monomeric. The protein inhibited proliferation of hepatoma HepG2 cells, colon cancer HT29 cells and breast cancer MCF-7 cells with an IC50 of about 1, 40 and 60µM, respectively. It inhibited HIV-1 reverse transcriptase with IC50 of 0.23µM. It inhibited mycelial growth in the fungus, Valsa mali. It did not exhibit hemagglutinating, ribonuclease, mitogenic or protease inhibitory activities.

Cape Town — The families of terminally ill patients are shunting their relatives back from Cape Town and other urban areas to the Eastern Cape before they die because it is cheaper for them to be transported alive rather than paying hefty undertaker's fees.And researchers say the return migration is largely due to the extremely high numbers of people infected with HIV.Patricia Fekema, a manager at Zusake Youth Support Group, an NGO in Du Noon township outside Cape Town, said there had been a "tremendous" increase in migration back to the Eastern Cape.

The New York City health department is warning residents about the dangers of receiving body-enhancement injections of castor oil and other substances.Dr. Nathan Graber, director of the health department's environmental and occupational disease program, says the department has been notified of five cases in the past two years involving injections of various oils to the hips, thighs, breasts and buttocks by unlicensed practitioners for cosmetic purposes. Similar cases have been reported in other cities and states.The substances used to enhance body parts include castor oil, silicone, petroleum jelly, mineral oil or cod liver oil.Those practices are illegal and unsafe, Graber says. The injections can cause serious infections, nerve damage, respiratory and kidney failure, irreversible disabilities, disfigurement and death. They also carry the risk of spreading infectious diseases such as HIV, hepatitis B and C.

HCV/HIV-coinfected persons are less likely to undergo a liver biopsy or be eligible for HCV therapy and are more likely to have treatment contraindications compared with HCV-monoinfected subjects. Strategies to address modifiable factors may enhance treatment eligibility in HCV-infected populations.

The results suggest that 350 cells per (mu)L should be the minimum threshold for initiation of antiretroviral therapy, and should help to guide physicians and patients in deciding when to start treatment.

DENVER, April 20 -- Some cancer patients who take green tea to fight the disease may have it backward: the popular dietary supplement actually blocks the effect of bortezomib (Velcade) and similar anticancer drugs, a researcher said here.

• Buy-out likely to cost Glaxo up to $3.6bn• Stiefel experts in skin treatments for acne and psoriasis

GlaxoSmithKline, Britain's biggest drugs company, has agreed to buy US drugmaker Stiefel Laboratories for up to $3.6bn (£2.5bn) in cash.The move comes as Glaxo aims to diversify from its best-selling pharmaceutical products into consumer products – Stiefel produces skin treatments for acne and psoriasis.The two companies will combine their dermatology businesses, creating a unit with $1.5bn of annual sales and 8% of the world market for prescription skin treatments, Glaxo said.Based in Coral Gables, Florida, Stiefel makes Soriatane, a pill to treat severe psoriasis – a chronic, noncontagious autoimmune disease that affects the skin and joints. Glaxo sells about $550m worth of prescription skin products a year.

Survival and predictors of outcomes in non-HIV-infected patients with extensively drug-resistant tuberculosis

There was high mortality in non-HIV-infected patients with XDR-TB at a TB referral hospital in South Korea. Adjunctive surgical treatment and linezolid improved the outcome for selected patients with XDR-TB.

Immunologic failure criteria performed poorly in this setting and would have resulted in a substantial proportion of participants with suppressed HIV-1 viral load being switched unnecessarily. These criteria also lacked sensitivity to identify participants failing virologically. Periodic viral load measurements may be a better marker for treatment failure in this setting.

Despite having similar demographic, socioeconomic, and nutritional status to Haitians, Africans infected with non-B clade HIV had slower rates of disease progression compared with both Haitians and Canadians, with both groups being infected by the clade B virus. The findings suggest that viral subtype may be an important predictor of HIV natural history in a developed medical setting.

Patterns of engagement in care by HIV-infected adults: South Carolina, 2004-2006

Large proportions of the South Carolina HIV-infected adult population are not consistently accessing HIV-medical care. Targeted programs are needed to improve engagement for HIV-infected adults most likely to transition or not be in care.

Stable frequency of HIV-1 transmitted drug resistance in patients at the time of primary infection over 1996-2006 in France

In this large study of patients at the time of primary infection, the frequency of acquired resistant virus was stable over time, over 5% for nucleoside/nucleotide reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor. One explanation for this stability may be the increasing number of treated patients in virological success.

With modern antiretroviral therapy, HIV positive people starting treatment today have an excellent chance of achieving a good response. But the situation is more challenging for highly treatment-experienced patients who have developed resistance to multiple drug classes and may require complex "salvage" regimens.

The first complete update in 5 years of the U.S. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-infected Adults and Adolescents has been released by the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC) in cooperation with the HIV Medicine Association of the Infectious Diseases Society of America (IDSA).

Some AIDS-defining Opportunistic Illnesses Remain a Significant Cause of Death in the HAART Era

Since the mid-1990s, combination antiretroviral therapy (ART) has dramatically reduced the risk of AIDS-related illness and death in people with HIV. But some opportunistic illnesses (OIs) remain a concern, according to a study by investigators with the Antiretroviral Therapy Cohort Collaboration published in the April 15, 2009 issue of Clinical Infectious Diseases.

What are the Next Practical Steps to Prevent or Reduce the Rate of New HIV Infections?

About 56,000 new cases of HIV infection have occurred annually in the U.S. over the past 10 years. Globally, in 2007 alone, the number of new infections was 2.7 million.Although vaccines have historically provided the most effective method of controlling the most lethal infectious diseases, thus far efforts to develop a safe and effective vaccine for preventing HIV infection have failed. So what is the current focus of policy-makers and researchers in terms of preventing new HIV infections in light of the well-publicized failure of recent vaccine trials?

In 2005, the average American consumed 64kg of added sugar, a sizeable proportion of which came through drinking soft drinks. Now, in a 10-week study, Peter Havel and colleagues, at the University of California at Davis, Davis, have provided evidence that human consumption of fructose-sweetened but not glucose-sweetened beverages can adversely affect both sensitivity to the hormone insulin and how the body handles fats, creating medical conditions that increase susceptibility to heart attack and stroke.

The initial CD4 cell counts of patients newly infected with HIV fell significantly between 1985 and 2001, US research published in the May 1st edition of Clinical Infectious Diseases has shown. This suggests that the virus may have evolved to become more virulent during this time period, which could have clinical implications, shortening the interval between infection with HIV and the need to start HIV treatment.

Starting HIV therapy improves some cardiovascular markers - but not all

Starting combination antiretroviral therapy improves markers of endothelial function but not arterial thickness and stiffness regardless of regimen type, says a new study reported in the April 15th issue of the Journal of Infectious Diseases. The small study provides insight into the mechanisms underlying the cardiovascular diseases that are becoming increasingly common among people with HIV on effective antiretroviral therapy.

Some advocates of the female condom hope that a new version of the product -- which is less expensive and more user-friendly -- will increase use and expand its role as a women-initiated method of protecting against HIV and other sexually transmitted infections, the AP/Long Island Newsday reports.

Female condom. Advocates hope to see greater use in global fight against AIDS

NEW YORK - Advocates of the female condom are promoting a less costly, more user-friendly version that they hope will vastly expand its role in the global fight against AIDS and other sexually transmitted diseases.An early version of the female condom was introduced in 1993, and it remains the only available woman-initiated form of protection against both STDs and unintended pregnancy. Yet despite global promotion by the United Nations and other organizations, its usage is still minuscule, even as women bear an ever-growing share of the AIDS epidemic.Advocates hope the dynamics will change following last month's approval by the Food and Drug Administration of the FC2, a new version of the female condom produced by the Chicago-based Female Health Co.

Raltegravir area-under-the curve level in cervicovaginal fluid (CVF) was equivalent to blood levels after multiple doses in HIV-negative volunteers. And half-life of the integrase inhibitor was more than twice as long in CVF as in blood. These findings and others led Amanda Jones and University of North Carolina colleagues to propose that raltegravir should be evaluated for postexposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP) in women.

n the April 15, 2009 photo, people are seen as they walk along a hallway past large signs at Merck & Company, Inc.'s world headquarters in Whitehouse Station, N.J. Drugmaker Merck & Co.

TRENTON, N.J. — Drugmaker Merck & Co. on Tuesday posted a 57 percent drop in first-quarter profit, falling short of expectations, because of a drop in both sales of its drugs and income from its partnership on cholesterol medicines.Last year's quarter also benefited from a one-time pretax gain of $2.2 billion from Merck's partnership with Britain's AstraZeneca PLC. Merck also said the global recession hurt results.

UNITAID and the Clinton HIV/AIDS Initiative have agreed a deal with generic drugs makers that should cut the cost of paediatric and second-line antiretroviral (ARV) medicines used in the treatment of HIV/AIDS.The deal, announced on Friday, should cut the price of one year's supply of the cheapest second-line ARVs by more than $100 to $590.

SAN DIEGO, April 21 /PRNewswire-FirstCall/ -- Aethlon Medical, Inc. (OTC Bulletin Board: AEMD - News), developer of the Hemopurifier®, a first-in-class medical device to treat infectious disease, today announced that it has hired RedChip Companies, Inc. to lead its investor relations outreach programs."We have created the first medical device that can selectively remove viruses from the bloodstream," stated James A. Joyce, chief executive officer of Aethlon Medical. "We plan to leverage RedChip's strong media, investor, and public relations platform to raise the visibility of our endeavors and expand our base of loyal shareholders," concluded Joyce. So far in 2009, the Aethlon Hemopurifier® has demonstrated significant viral load reductions in both Hepatitis-C (HCV) and HIV infected patients."We are thrilled to have the opportunity to represent Aethlon Medical, a company that is making such groundbreaking advances in the field of virus treatment," said Dave Gentry, president and chief executive officer of RedChip Companies, Inc. "We look forward to introducing Aethlon to RedChip's investor network as we launch a comprehensive investor relations program."

Patients should have a blood level of 25(OH)D tested once a year, ideally at the end of the Fall season, to ensure that they are not vitamin D deficient before Winter. This will prevent many of the complications associated with vitamin D deficiency.

About 20-30% of persons with HIV infection, especially those living in countries with limited resources, experience an immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral treatment. The active form of vitamin D, 1,25-dihydroxyvitamin D, is a key player in clearance of pathogens and influences the level of inflammation and macrophage activation.

Some diabetes guidelines set low glycemic control goals for patients with type 2 diabetes mellitus (such as a hemoglobin A1c level as low as 6.5% to 7.0%) to avoid or delay complications. Our review and critique of recent large randomized trials in patients with type 2 diabetes suggest that tight glycemic control burdens patients with complex treatment programs, hypoglycemia, weight gain, and costs and offers uncertain benefits in return. We believe clinicians should prioritize supporting well-being and healthy lifestyles, preventive care, and cardiovascular risk reduction in these patients. Glycemic control efforts should individualize hemoglobin A1c targets so that those targets and the actions necessary to achieve them reflect patients' personal and clinical context and their informed values and preferences.

A Systematic Review of the Evidence Supporting a Causal Link Between Dietary Factors and Coronary Heart Disease

The evidence supports a valid association of a limited number of dietary factors and dietary patterns with CHD. Future evaluation of dietary patterns, including their nutrient and food components, in cohort studies and randomized trials is recommended.

Raltegravir area-under-the curve level in cervicovaginal fluid (CVF) was equivalent to blood levels after multiple doses in HIV-negative volunteers [1]. And half-life of the integrase inhibitor was more than twice as long in CVF as in blood. These findings and others led Amanda Jones and University of North Carolina colleagues to propose that raltegravir should be evaluated for postexposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP) in women.

Legislators suggested today that they are exploring ways to head off proposed co-payments for some AIDS/HIV patients who get their medications through the state as part of Governor Corzine’s new budget.

Deutsche AIDS-Hilfe, the largest HIV voluntary sector organisation in Germany has issued a position paper on the role of treatment in HIV prevention which broadly echoes and supports last year’s landmark Swiss statement on the limited risk of a person taking effective HIV treatment passing on their infection

Rheumatologic symptoms after ART may be due to immune reconstitution inflammatory syndrome (IRIS)

New or worsening rheumatologic symptoms that follow antiretroviral therapy may be due to immune reconstitution inflammatory syndrome (IRIS), according to findings reported at the Fourth South African AIDS Conference in Durban.

Home stimulation programme shows positive impacts on the neurodevelopmental status of children infected with HIV

Participation in a basic home stimulation programme can lead to improvements in both motor and cognitive development in HIV-positive children under 30 months, according to findings from a study presented at the Fourth South African AIDS Conference in Durban in early April.

Interferon-based Therapy for Hepatitis C Improves Fibrosis Even in Individuals without Virological Response

Successful treatment with interferon-based therapy can clear hepatitis C virus (HCV) and slow or halt liver disease progression, but studies have produced conflicting results with regard to improvement or reversal of existing liver fibrosis.

Several studies have shown that people with chronic hepatitis C have an increased risk of developing insulin resistance and diabetes mellitus, but it is not clear whether this excess risk can be reduced with interferon-based therapy.

Due to overlapping transmission routes, a minority of people with HIV are also coinfected with hepatitis B virus (HBV). In addition to those with measurable hepatitis B surface antigen (HBsAg), some patients have "occult" or hidden HBV, characterized by low-level detectable HBV DNA in individuals with HBV core antibodies (anti-HBc) but without HBsAg.

Long-term outcome of tenofovir disoproxil fumarate use against hepatitis B in an HIV-coinfected cohort

TDF was able to control HBV replication in most HIV-coinfected patients after a median follow-up duration of 34 months, regardless of previous lamivudine treatment. However, a sizeable proportion of patients developed virological breakthrough.

Systematic sequence analysis of human immunodeficiency virus type 1 (HIV-1) variants with RNA levels underestimated by the Cobas TaqMan HIV-1 assay demonstrated that mutations at a single position of the downstream primer can lead to the underestimation of HIV-1 RNA levels by more than 2 log and to false-negative results in minipool screening of blood donors. Mutations at this position are found in about 2% of all HIV-1 M gag sequences.

Meta-analysis: Prevalence of HIV Infection and Syphilis among MSM in China

MSM are a high risk population for HIV infection in China. An effective strategy for prevention and control is required for this specific population. Differences between sampling methods, sample sizes and study locations may explain some of the inconsistencies found in the included studies.

High prevalence of risk behavior concurrent with links to other high risk populations: a potentially explosive HIV epidemic among men who have sex with men in Guangzhou, China

HIV has been introduced into MSM in Guangzhou. The risk factors both on the demographic and behavior and the overlapped risky population would contribute to a potential explosive of HIV among MSM, even bridge to female population in Guangzhou if none timely and effective response is implemented.

Risk and prognostic significance of tuberculosis in patients from The TREAT Asia HIV Observational Database

The risk of TB diagnosis was associated with increasing immunodeficiency and partly reduced by antiretroviral treatment. The prognosis of developing TB appeared to be similar to that following a diagnosis of other non-TB ADI.

A singer from the German girl band No Angels arrested on suspicion of infecting a partner with HIV has been released from custody, BBC reported.Prosecutors say Nadja Benaissa, 26, had unprotected sex with three men without informing them she was infected, and that one later tested positive himself.Ms Benaissa's lawyers said she should enjoy the presumption of innocence.A spokesman for a court in the town of Darmstadt said her release was subject to certain undisclosed conditions.Ms Benaissa was arrested in Frankfurt 10 days previously, before she was due to perform in a solo concert.The prosecutor's office in the western town of Darmstadt said she had been detained because of the "urgent suspicion" that she slept with three people between 2004 and 2006, without telling them she was HIV-positive.She reportedly faces a possible charge of grievous bodily harm.But her lawyers note that there is no proof that she infected anyone.Benaissa was chosen to join No Angels in 2000 through the TV casting show Popstars.The group recorded a series of hits and emerged as Germany's most successful girl band.

In the past two years, through the leadership of Ryan Clary, our Public Policy Director, Project Inform has become heavily involved in work to increase the government response to the grossly ignored U.S. epidemic of hepatitis C (HCV). Matt Sharp, our new Director of Treatment & Prevention Advocacy, is now monitoring drug development in this area and will help guide our work to educate people with hepatitis C about treatment options.

A HIV-positive taxi driver twice found guilty of raping a teenaged female passenger has been jailed for nine years.Abdirazak Yussuf Mussa, 56, was originally found guilty in November 2007 of rape and abduction with intent to sexually violate and jailed for seven years.The Court of Appeal last year quashed the conviction and ordered a retrial.Last month he was again found guilty of raping the woman but not guilty of abduction.

This study examined the prevalence and characteristics of attempted suicide among a representative sample of French Human Immunodeficiency virus (HIV) infected individuals. In 2003, a face-to-face survey was conducted among people living with HIV/AIDS (PLWHA) selected in a random, stratified sample of French hospital departments. Among solicited individuals, 2,932 agreed to participate and were asked if they had ever AS. Among the respondents, 23% had AS. Female gender, younger age, native French citizenship, reporting household financial difficulties, having been HIV-contaminated through homosexual contact or through injection drug use and suffering from lipodystrophy-related symptoms were all independently associated with AS. HIV-discrimination and the lack of social support from family remained independently associated with AS. Our findings indicate a high level of AS among PLWHA and emphasize the multiple roles of factors associated with living with HIV, together with sociodemographic factors. The results enable the possibility for vulnerable groups to be targeted for specific future interventions in order to prevent attempted suicide.

Note (John2038)To access the article directly, search for it typing "Suicide attempts among people living with HIV in France". The URLs of this website are not compatible with the posting syntax used on this board.

We examined whether two functional polymorphisms (g.-1562C>T and g.-90(CA)14–24) in the matrix metalloproteinase (MMP)-9 gene or MMP-9 haplotypes affect the circulating levels of pro-MMP-9 and pro-MMP-9/TIMP-1 (tissue inhibitor of metalloproteinase-1) ratios in AIDS patients, and modulate alterations in these biomarkers after highly active antiretroviral therapy (HAART). We studied 82 patients commencing HAART. Higher pro-MMP-9 concentrations and pro-MMP-9/TIMP-1 ratios were found in CT/TT patients compared with CC patients. HAART decreased pro-MMP-9 levels and pro-MMP-9/TIMP-1 ratios in CT/TT patients, it did not modify pro-MMP-9 levels and it increased pro-MMP-9/TIMP-1 ratios in CC patients. The g.-90(CA)14–24 polymorphism, however, produced no significant effects. Moreover, we found no significant differences in HAART-induced changes in plasma pro-MMP-9, TIMP-1 and pro-MMP-9/TIMP-1 ratios when different MMP-9 haplotypes were compared. These findings suggest that the g.-1562C>T polymorphism affects pro-MMP-9 levels in patients with AIDS and modulates the alterations in pro-MMP-9 levels caused by HAART, thus possibly affecting the risk of cardiovascular complications.

Study on the Inhibitory Mechanism and Binding Mode of the Hydroxycoumarin Compound NSC158393 to HIV-1 Integrase by Molecular Modeling

Human immunodeficiency virus type 1 (HIV-1) integrase (IN) is an essential enzyme in the life cycle of this virus and also an important target for the study of anti-HIV drugs. In this work, the binding modes of the wild type IN core domain and the two mutants, i.e. W132G and C130S, with the 4-hydroxycoumarin compound NSC158393 were evaluated by using the relaxed complex molecular docking approach combained with molecular dynamics (MD) simulations. Based on the monomer MD simulations, both of the two substitutions affect not only the stability of the 128-136 peptide, but also the flexibility of the functional 140s loop. In principle, NSC158393 binds the 128-136 peptide of IN, however, the specific binding modes for the three systems are various. According to the binding mode of NSC158393 with WT, NSC158393 can effectively interfere with the stability of the IN dimer by causing a steric hindrance around the monomer interface. Additionally, through the comparative analysis of the MD trajectories of the wild type IN and the IN-NSC158393 complex, we found that NSC15893 may also exert its inhibitory function by diminishing the mobility of the function loop of IN. Three key binding residues, i.e.W131, K136 and G134, were discovered by energy decomposition calculated with the MM-GBSA method. Characterized by the largest binding affinity, W131 is likely to be indispensable for the ligand binding. All the above results are consistent with experiment data, providing us some helpful information for understanding the mechanism of the coumarin-based inhibitors

Absence of genotypic drug resistance and presence of several naturally occurring polymorphisms of human immunodeficiency virus-1 CRF06_cpx in treatment-naive patients in Estonia

All non-B HIV-1 subtypes and circulating recombinant forms (CRFs) are characterized by several polymorphisms in protease (PR) region. In addition, in recent years the increasing use of antiretroviral treatment (ART) has rapidly raised the spread of transmitted drug resistance. We aimed to determine the presence of naturally occurring polymorphisms and transmitted drug resistance mutations (DRMs) in ART naïve HIV-1-positive subjects in Estonia. A total of 115 drug-naive HIV-1-infected subjects (mean age 27 years; 70% male; 65% infected via intravenous drug use and 34% by heterosexual contact) were enrolled. Viral genomic RNA from plasma was directly sequenced in PR, revertase (RT), and envelope (env) regions. Phylogenetic analysis of RT and env regions revealed that 89% and 3% of sequenced viruses belonged to CRF06_cpx and subtype A1, respectively, and 6% were described as unique recombinants (signed A1-06) between CRF06_cpx and subtype A1 viruses. No primary DRMs were found in PR or RT regions indicating the absence of transmitted drug resistance. The most common polymorphisms in the PR region were K14R, M36I, H69K, and L89M seen in 96%, 100%, 99%, and 100%, respectively. The clinical relevance of these polymorphisms in terms of success of ART has to be monitored in future clinical studies. J. Med. Virol. 81:953-958, 2009.

Autonomous Regulation and Locus of Control as Predictors of Antiretroviral Medication Adherence

The purpose of the current study was to examine the interrelationships between autonomous regulation (AR) and locus of control (LOC) and their prediction of Antiretroviral Therapy (ART) adherence among 189 HIV+ patients. Path analyses revealed that neither AR nor LOC directly predicted adherence although AR was indirectly related when mediated by self-efficacy. AR was positively related to internal and doctors LOC, but not related to chance or others LOC. Overall, results support Self-determination Theory's conceptualization of AR and indicate that AR may be a more robust predictor of medication adherence than LOC variables.

Virco Lab, Inc. a leader in HIV resistance testing services, is pleased to announce a US collaboration with SmartGene, Inc. a provider of novel services for the management and analysis of genetic data to provide laboratories and physicians with greater insight into HIV drug resistance and to transfer the ordering, viewing and storage of HIV resistance reports to an innovative secure Web-based system.

Improving Taiwanese adolescents’ HIV/AIDS preventive self-efficacy could be useful to reduce risky sexual behaviors in this population. Results of this study may assist nurses in understanding factors related to adolescents HIV/AIDS related risky sexual behavior and its’ preventions. However, future longitudinal studies are needed to clarify whether depressive symptoms is a major influential factor that might interfere with the effectiveness of HIV/AIDS prevention programs.

HIV-1–associated nephropathy (HIVAN) is a common complication of HIV-1 infection, and its skewed incidence in certain ethnic groups suggests that there is a genetic basis to HIVAN susceptibility. In their study reported in this issue of the JCI, Papeta and colleagues used a combination of gene expression profiling and linkage analysis to identify three genomic loci that regulate a network of genes expressed by podocytes — cells that are crucial to the filtration of fluid and waste by the kidney (see the related article, doi:10.1172/JCI37131). Surprisingly, two of these loci confer disease susceptibility in a transgenic mouse model of HIVAN. This report confirms the central role of podocytes in the pathogenesis of HIVAN and demonstrates the power of this combination of genomic analysis techniques in elucidating the pathogenesis of glomerular disease.

Some studies have suggested that as the HIV epidemic progresses, infected patients are presenting at progressively lower CD4-cell counts, perhaps reflecting an increase in the virulence of the virus. However, the results have been inconsistent and often confounded by a lack of information about known dates of seroconversion.The U.S. military provides a unique opportunity to study this issue because active-duty personnel are screened for infection at regular intervals and thus have reliable seroconversion windows. In the Tri-Service AIDS Clinical Consortium, investigators evaluated initial CD4-cell counts (assessed within 6 months of HIV diagnosis) among 2174 treatment-naive individuals with documented HIV seroconversions between 1985 and 2007.